Boron-containing cyclic release compound and color-changing film containing the same

Abstract

The present disclosure relates to novel photoluminescent complexes comprising a BODIPY moiety covalently linked to a blue light absorbing moiety, and color conversion films and backlight units employing the same.

Description

[Technical Field]

[0001] [Cross-reference of related applications] This application claims priority to U.S. Provisional Patent Application No. 63 / 152,309, filed on 22 February 2021, and U.S. Provisional Patent Application No. 63 / 278,904, filed on 12 November 2021, which together constitute a part of this specification. [Background technology]

[0002] In color reproduction, gamut, or color space, is a specific, complete subset of colors available on a device such as a television or monitor. For example, Adobe® Red, Green, Blue (RGB) is a wide-gamut color space achieved by using pure spectral primary colors. It was developed to provide a wider color space and a more realistic representation of visible colors seen through a display. It is believed that devices capable of providing a wider color gamut can enable displays to depict more vibrant colors.

[0003] As high-definition, large-screen displays become commonplace, there is a growing demand for higher-performance, thinner, and more feature-rich displays. Current light-emitting diodes (LEDs) produce a white light source by exciting a green, red, or yellow phosphor with a blue light source. However, the full width at half maximum (FWHM) of the emission peaks of current green and red phosphors is very large, usually exceeding 40 nm, resulting in overlapping of the green and red spectra, leading to color rendering where they cannot be completely distinguished from each other. This overlap leads to low color rendering and a reduced color gamut.

[0004] To compensate for the reduction in color gamut, a method has been developed that uses films containing quantum dots in combination with LEDs. However, there are problems with the use of quantum dots. Firstly, cadmium-based quantum dots are extremely toxic and have been banned in many countries due to health and safety concerns. Secondly, non-cadmium-based quantum dots have very low efficiency in converting blue LED light into green and red light. Thirdly, quantum dots require an expensive encapsulation process to protect them from moisture and oxygen. Finally, the cost of using quantum dots is high because it is difficult to control size uniformity during the manufacturing process.

[0005] Therefore, there is a need to improve the performance of color conversion films, backlight units, and display devices. [Overview of the project]

[0006] The photoluminescent complexes described herein can be used to improve the contrast between distinguishable colors in televisions, computer monitors, smart devices, and any other devices that utilize color displays. The photoluminescent complexes of this disclosure have good blue light absorption and a narrow emission bandwidth, providing novel color-converting dye complexes having, for example, an emission bandwidth full width at half maximum (FWHM) of less than 40 nm. In some embodiments, the photoluminescent complex absorbs light of a first wavelength and emits light of a second wavelength higher than the first wavelength. The photoluminescent complexes disclosed herein can be used in color-converting films used in light-emitting devices. The color-converting films of this disclosure provide high color rendering by reducing color degradation by reducing overlap in the color spectrum.

[0007] In some embodiments, the photoluminescent complex may include a blue light absorbing moiety, a linker complex which is a substituted ester, an unsubstituted ester, a substituted ether, or an unsubstituted ether, and a boron-dipyromethene (BODIPY) moiety. In some embodiments, the blue light absorbing moiety is a xanthenoizoquinoline derivative. In some embodiments, the linker complex may covalently bond the xanthenoizoquinoline derivative to the BODIPY moiety. In some embodiments, the xanthenoizoquinoline derivative absorbs light of a first excitation wavelength and transfers the energy to the BODIPY moiety. In some embodiments, the BODIPY moiety absorbs energy from the xanthenoizoquinoline derivative and emits light energy of a second, higher wavelength.

[0008] In some embodiments, the blue light absorbing portion is a naphthalimide derivative. In some embodiments, the linker complex can covalently bond the naphthalimide derivative to the BODIPY portion. In some embodiments, the naphthalimide derivative absorbs light of a first excitation wavelength and transfers the energy to the BODIPY portion. In some embodiments, the BODIPY portion absorbs energy from the naphthalimide derivative and emits light energy of a second, higher wavelength.

[0009] In some embodiments, the photoluminescent complex has an emission quantum yield of more than 80%. In some embodiments, the photoluminescent complex may have an emission band with a full width at half maximum (FWHM) of up to 40 nm.

[0010] In some embodiments, the photoluminescent complex may have a Stokes shift of 45 nm or more, which is the difference between the excitation peak of the blue light absorption portion and the emission peak of the BODIPY portion.

[0011] In some embodiments, the xanthenoizoquinoline derivative may have the following general formula: [Chemical formula] (wherein each R , 6 , 5 , , 4 , , 3 , 1 , , , n , 2 , and R 10 is independently hydrogen (H), a C1-C4 alkyl group, a trifluoromethyl group, an alkoxy group, -(OCH2CH2) n -OCH3 (wherein n is 1, 2, 3, or 4), or an optionally substituted aryl group).

[0012] In some embodiments, the naphthalimide derivative can be of the following general formula: [Chemical formula] (wherein each R <​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​-OCH3 (wherein n is 1, 2, 3, or 4), alkyl ester, or aryl ester. In some embodiments, R 7 and R 8 This can be hydrogen (H), a methyl group, a halide, or a C1-C3 alkoxy group.

[0014] Several embodiments include a color-converting film. In some examples, the color-converting film may include a color-converting layer comprising a resin matrix and a photoluminescent complex as described herein dispersed within the resin matrix. In some embodiments, the color-converting film may have a thickness between 1 μm and about 200 μm. In some embodiments, the color-converting film of the Disclosure may absorb blue light in the range of 400 nm to about 480 nm and emit light in the wavelength range of 500 nm to about 560 nm. Another embodiment includes a color-converting film that may absorb blue light in the range of 400 nm to about 480 nm and emit light in the wavelength range of 575 nm to about 645 nm. In some embodiments, the color-converting film may further comprise a transparent substrate layer. In some embodiments, the transparent substrate layer comprises two opposing surfaces, and the color-converting layer is disposed on one of the opposing surfaces.

[0015] In some embodiments, the color-converting film of the present disclosure may include a singlet oxygen quencher. In some embodiments, the color-converting film may further include a free radical scavenger.

[0016] Some embodiments include a method for producing a color-converting film, which comprises dissolving the aforementioned photoluminescent complex and binder resin in a solvent and coating the mixture onto one of the opposing surfaces of a transparent substrate.

[0017] Some embodiments include a backlight unit comprising the color conversion film described herein.

[0018] Some embodiments include display devices comprising the backlight unit described herein.

[0019] This application provides a photoluminescent complex having excellent color gamut and luminescence characteristics, a method for manufacturing a color conversion film using the photoluminescent complex, and a backlight unit comprising the color conversion film. These embodiments and other embodiments are described in detail below. [Brief explanation of the drawing]

[0020] [Figure 1] This graph shows the absorption spectrum of one embodiment (PLC-1) of the photoluminescent complex. [Figure 2] This graph shows the emission spectrum of one embodiment (PLC-1) of the photoluminescent complex. [Figure 3] This graph shows the absorption and emission spectra of one embodiment (PLC-2) of the photoluminescent complex. [Modes for carrying out the invention]

[0021] This disclosure relates to photoluminescent compounds and complexes used in color conversion films, backlight units, and display devices.

[0022] This disclosure describes photoluminescent complexes and their use in color conversion films. Photoluminescent complexes can be used to improve and enhance the transmission of one or more desired emission bandwidths within a color conversion film. In some embodiments, a photoluminescent complex can enhance the transmission of a desired first emission bandwidth while reducing the transmission of a second emission bandwidth. For example, a color conversion film can enhance the contrast or intensity between two or more colors, improving their distinguishability from one another. This disclosure includes photoluminescent complexes capable of enhancing the contrast or intensity between two colors, improving their distinguishability from one another.

[0023] Where a compound or chemical structure is referred to as "substituted" as used herein, it may include one or more substituents. The substituted group is derived from an unsubstituted parent structure, in which one or more hydrogen atoms on the parent structure are independently replaced by one or more substituents. In one or more forms, the substituents may be independently selected from optionally substituted alkyl, alkenyl, or C3-C7 heteroalkyl groups.

[0024] The alkyl moiety may be branched, linear (i.e., unbranched), or cyclic. In some embodiments, the alkyl moiety may have 1 to 8 carbon atoms. Alkyl groups of compounds specified herein may be designated as "C1-C8 alkyl" or similar designations. As merely an example, "C1-C8 alkyl" indicates that the alkyl chain contains 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms, i.e., the alkyl chain is methyl, ethyl, propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, and any isomers thereof. Thus, C1-C8 alkyl includes C1-C2 alkyl, C1-C3 alkyl, C1-C4 alkyl, C1-C5 alkyl, C1-C6 alkyl, C1-C7 alkyl, and C1-C8 alkyl. Alkyl groups may be substituted or unsubstituted. Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0025] As used herein, the term "heteroalkyl" refers to an alkyl group, as defined herein, in which one or more constituent carbon atoms are replaced by nitrogen, oxygen, or sulfur. Examples include, but are not limited to, -CH2-O-CH3, -CH2-CH2-O-CH3, -CH2-NH-CH3, -CH2-N(CH3)-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, and -CH2-CH2-S(O)-CH3. Furthermore, up to two heteroatoms may be consecutive, for example, -CH2-NH-O-CH3.

[0026] The term "aromatic" refers to a planar ring having a delocalized π-electron system containing 4n+2 (where n is an integer) π-electrons. Aromatic rings can be formed from 5, 6, 7, 8, 9, or 10 or more atoms. Aromatic rings may be optionally substituted. The term "aromatic" includes both carbocyclic aryl (e.g., phenyl) and heterocyclic aryl (i.e., "heteroaryl" or "heteroaromatic") groups (e.g., pyridine). The term includes monocyclic or fused polycyclic (i.e., rings sharing pairs of adjacent carbon atoms) groups.

[0027] The term "hydrocarbon ring" refers to a monocyclic or polycyclic ring or ring system containing only carbon and hydrogen, and can be saturated. Monocyclic hydrocarbon rings contain groups with 3 to 12 carbon atoms. Examples of monocyclic groups include the following: [ka] Examples include the following: [ka] These are some examples.

[0028] As used herein, the term "aryl" refers to an aromatic ring in which each of the ring-forming atoms is a carbon atom. An aryl ring may be formed by five, six, seven, eight, or nine or more carbon atoms. The aryl group may be substituted or unsubstituted. Examples of aryl groups include, but are not limited to, phenyl, naphthalenyl, and phenantrenyl.

[0029] The term "aralkyl" refers to an alkyl group substituted with an aryl group. Examples of non-restrictive aralkyl groups include benzyl and phenethyl.

[0030] The term "heteroaryl" refers to an aryl group containing one or more ring heteroatoms selected from nitrogen, oxygen, and sulfur, and a heteroaryl group has 4 to 10 atoms in its ring system. It is understood that a heteroaryl ring can have additional heteroatoms within the ring. In a heteroaryl having two or more heteroatoms, those two or more heteroatoms may be the same or different from each other. Heteroaryls can be optionally substituted. A nitrogen-containing heteroaryl moiety refers to an aryl group in which the ring skeleton atom is a nitrogen atom. Examples of heteroaryl groups include the following: pyrrole, imidazole, etc.

[0031] As used herein, the term "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0032] As used herein, the terms “bond,” “bonded,” “direct bond,” or “single bond” mean a chemical bond between two atoms or between two parts where the atoms joined by the bond are considered to be part of a larger structure.

[0033] As used herein, the term “part” refers to a specific segment or functional group of a molecule. A chemical part is often perceived as a chemical component embedded within or added to a molecule.

[0034] As used herein, the terms "cyano" or "nitrile" refer to any organic compound containing a -CN functional group.

[0035] The term "ester" refers to a chemical part having the formula -COOR (wherein R includes alkyl, cycloalkyl, aryl, heteroaryl (linked via a ring carbon), and heterocyclic (linked via a ring carbon)). Any hydroxyl or carboxyl side chain on the compounds described herein may be esterified. Any suitable procedure and specific group can be used to prepare such esters.

[0036] As used herein, the term "ether" refers to a chemical moiety having the general formula RO-R' (wherein R and R' are alkyl and / or aryl), containing an oxygen atom bonded to two alkyl or aryl groups. Similarly, the term "alkoxy" refers to a chemical moiety containing an oxygen atom bonded to an alkyl group further bonded to an alkyl or aryl group.

[0037] As used herein, the term "ketone" refers to a chemical part comprising a carbonyl group (carbon-oxygen double bond) connected to two alkyl or aryl groups having the general formula RC(=O)R' (wherein R and R' are alkyl and / or aryl).

[0038] As used herein, the term "BODIPY" is defined by the following formula: [ka] This refers to the chemical part that possesses [certain properties].

[0039] The BODIPY portion can consist of dipyromethene complexed with a disubstituted boron atom, typically a BF2 unit. The IUPAC name for the BODIPY core (i.e., without any substituents) is 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene.

[0040] As used herein, the terms "xanthenoisoquinoline" or "xanthenoisoquinoline derivative" refer to the formula: [ka] This refers to a chemical part having a specific characteristic, such as 1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione.

[0041] As used herein, the terms “naphthalimide” or “naphthalimide derivative” refer to the formula: [ka] This refers to the chemical part that possesses the characteristic feature.

[0042] This disclosure relates to a photoluminescent complex that absorbs light energy at a first wavelength and emits light energy at a second, higher wavelength. The photoluminescent complex of this disclosure comprises an absorber-emitting portion and an emitter-emitting portion coupled via a linker, the distance between them being adjusted so that the absorber-emitting portion transfers its energy to an acceptor-emitting portion, which then emits at a second wavelength greater than the absorbed first wavelength.

[0043] In some embodiments, the photoluminescent complex comprises a blue light absorbing moiety, a linker complex, and a boron-dipyromethene (BODIPY) moiety. In some embodiments, the blue light absorbing moiety is a xanthenoizoquinoline derivative. In some embodiments, the linker complex can covalently bond the xanthenoizoquinoline derivative to the BODIPY moiety. In some embodiments, the xanthenoizoquinoline derivative absorbs light of a first excitation wavelength, transferring the energy to the BODIPY moiety, which then emits light energy of a second wavelength, where the light energy of the second wavelength is higher than that of the first wavelength.

[0044] In some embodiments, the blue light absorbing portion is a naphthalimide derivative. In some embodiments, the linker complex can covalently bond the naphthalimide derivative to the BODIPY portion. In some embodiments, the naphthalimide derivative absorbs light of a first excitation wavelength, transferring the energy to the BODIPY portion, which then emits light energy of a second wavelength, where the energy of the second wavelength is higher than that of the first wavelength.

[0045] Energy transfer from the excited xanthenoizoquinoline derivative or naphthalimide derivative to the BODIPY moiety is thought to occur via Forster resonance energy transfer (FRET). This idea is based on the absorption / emission spectrum of the photoluminescent complex, which has two main absorption bands: one in the blue light absorption band (xanthenoizoquinoline derivative or naphthalimide derivative) and the other in the BODIPY absorption band, with only one emission band at the emission wavelength of the BODIPY moiety (see Figures 1 and 2).

[0046] In some embodiments, the photoluminescent complex may have a high emission quantum yield. In some embodiments, the emission quantum yield may exceed 50%, 60%, 70%, 80%, or 90%. In some embodiments, the emission quantum yield may exceed 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. The emission quantum yield can be measured by dividing the number of emitted photons by the number of absorbed photons, which is equal to the emission efficiency of the emission portion. In some embodiments, the absorption emission portion may have an emission quantum yield of more than 80%. In some embodiments, the quantum yield may be greater than 0.8 (80%), 0.81 (81%), 0.82 (82%), 0.83 (83%), 0.84 (84%), 0.85 (85%), 0.86 (86%), 0.87 (87%), 0.88 (88%), 0.89 (89%), 0.9 (90%), 0.91 (91%), 0.92 (92%), 0.93 (93%), 0.94 (94%), or 0.95 (95%), and may be close to 1 (100%). Quantum yield measurements in the film can be performed using a spectrophotometer, such as the Quantaurus-QY spectrophotometer (Hamamatsu, Inc., Campbell, California, USA).

[0047] In some embodiments, the photoluminescent complex has an emission band that may have a full width at half maximum (FWHM) of less than 40 nm. FWHM is the width of the emission band in nanometers at an emission intensity that is half the maximum emission intensity for the band. In some embodiments, the photoluminescent complex has FWHM values ​​for emission bands of about 35 nm or less, about 30 nm or less, about 25 nm or less, and about 20 nm or less.

[0048] In some embodiments, the photoluminescent complex may have a Stokes shift of 45 nm or greater. As used herein, the term "Stokes shift" means the distance between the excitation peak of the blue light absorption moiety and the emission peak of the BODIPY moiety.

[0049] The photoluminescent complexes of this disclosure may have a tunable emission wavelength. By substituting the BODIPY moiety with different substituents, the emission wavelength can be tuned to a value between approximately 500 nm and approximately 560 nm, or any value limited by this range.

[0050] In some embodiments, the blue light absorbing portion may have a peak absorption maximum between wavelengths of about 400 nm and about 470 nm. In some embodiments, the peak absorption may be at any wavelength between about 400 nm and about 405 nm, about 405 nm and 410 nm, about 410 nm and 415 nm, about 415 nm and 420 nm, about 420 nm and 425 nm, about 425 nm and 430 nm, about 430 nm and 435 nm, about 435 nm and 440 nm, about 440 nm and 445 nm, about 445 nm and 450 nm, about 450 nm and 455 nm, about 455 nm and 460 nm, about 460 nm and 465 nm, about 465 nm and 470 nm, or within a range limited by any of these values.

[0051] In some embodiments, the photoluminescent complex may have an emission peak between about 500 nm and about 560 nm. In some embodiments, the emission peak may be at any wavelength between about 500 nm and about 515 nm, about 515 nm and about 520 nm, about 520 nm and about 525 nm, about 525 nm and about 530 nm, about 530 nm and about 535 nm, about 535 nm and about 540 nm, about 540 nm and about 545 nm, about 545 nm and about 550 nm, about 550 nm and about 555 nm, about 555 nm and about 560 nm, or any wavelength within a range limited by any of these ranges.

[0052] Some embodiments include a photoluminescent complex in which the spatial distance between the blue light-absorbing xanthenoizoquinoline or derivative and the BODIPY moiety is regulated via a linker complex for energy transfer of the blue light-absorbing xanthenoizoquinoline derivative to the BODIPY moiety.

[0053] Other embodiments include a photoluminescent complex in which the spatial distance between the blue light-absorbing naphthalimide derivative and the BODIPY moiety is regulated via a linker complex for energy transfer of the blue light-absorbing naphthalimide derivative to the BODIPY moiety.

[0054] This disclosure includes a photoluminescent complex (PLC), which may comprise a blue light-absorbing xanthenoizoquinoline derivative, a linker complex, and a BODIPY moiety. The linker complex covalently bonds the blue light-absorbing xanthenoizoquinoline derivative and the BODIPY moiety. In some embodiments, the xanthenoizoquinoline derivative absorbs light energy at a first excitation wavelength and transfers the energy to the BODIPY moiety, which absorbs energy from the xanthenoizoquinoline derivative and emits light energy at a second, higher wavelength, and the photoluminescent complex has an emission quantum yield of more than 80%.

[0055] Some embodiments include a blue light absorbing xanthenoizoquinoline derivative, the blue light absorbing xanthenoizoquinoline derivative having the following general formula: [ka] (In the formula, R 0 and R 10 This includes hydrogen (H), C1-C4 alkyl groups (e.g., methyl, n-butyl, t-butyl, etc.), trifluoromethyl groups, optionally substituted aryl groups, and -(OCH2CH2) n It may be -OCH3 (wherein n is 1, 2, 3, or 4), or an alkoxy group.

[0056] In some embodiments, R 10 C is a compound of methyl, ethyl, n-propyl, isopropyl, butyl, t-butyl, etc. 1~4 It is alkyl.

[0057] In some embodiments, R 10 It is t-butyl.

[0058] In some embodiments, R 10 is unsubstituted phenyl, [ka] It is possible.

[0059] In some embodiments, R 10 R can be an unsubstituted phenyl. In some embodiments, R 10 teeth, [ka] It is possible. In some embodiments, R 10 teeth, [ka] It is possible. In some embodiments, R 10 teeth, [ka] It is possible. In some embodiments, R 10 teeth, [ka] It is possible. In some embodiments, R 10 teeth, [ka] It is possible. In some embodiments, R 10 teeth, [ka] It is possible. In some embodiments, R 10 teeth, [ka] It is possible. In some embodiments, R 10 teeth, [ka] It is possible.

[0060] In some embodiments, R 10 This is not limited to, but includes methoxy(-OMe), or [ka] It may contain an alkoxy moiety.

[0061] In some embodiments, R 10 R may be methoxy. In some embodiments, R 10 teeth, [ka] It is possible.

[0062] Several embodiments include a photoluminescent complex (PLC), which may comprise a blue light-absorbing naphthalimide derivative, a linker complex, and a BODIPY moiety. The linker complex covalently bonds the blue light-absorbing naphthalimide derivative and the BODIPY moiety. In some embodiments, the naphthalimide derivative absorbs light energy at a first excitation wavelength and transfers the energy to the BODIPY moiety, which absorbs energy from the naphthalimide derivative and emits light energy at a second, higher wavelength. In such embodiments, the photoluminescent complex has an emission quantum yield of more than 80%.

[0063] Some embodiments include a blue light absorbing naphthalimide derivative, the blue light absorbing naphthalimide derivative having the following general formula: [ka] (In the formula, R 0 and R 10 This may be a xanthenoizoquinoline derivative (as defined above).

[0064] The linker complex covalently bonds a blue-absorbing xanthenoizoquinoline derivative (or naphthalimide derivative) to the BODIPY moiety. The linker complex can be adjusted to control the spatial distance between the blue-absorbing xanthenoizoquinoline derivative (or naphthalimide derivative) and the BODIPY moiety. By adjusting the spatial distance between the xanthenoizoquinoline derivative (or naphthalimide derivative) and the BODIPY, the quantum yield can be adjusted. In some embodiments, the distance separating the blue-absorbing xanthenoizoquinoline derivative (or naphthalimide derivative) and the BODIPY moiety may be about 8 Å or less. The linker complex can maintain the distance between the blue-absorbing xanthenoizoquinoline derivative (or naphthalimide derivative) and the BODIPY moiety.

[0065] In some embodiments, the photoluminescent complex includes a linker complex, which covalently bonds a blue light-absorbing xanthenoizoquinoline derivative to the BODIPY moiety. In some embodiments, the linker complex may include a single bond between the xanthenoizoquinoline derivative and the BODIPY moiety.

[0066] In many embodiments, the photoluminescent complex includes a linker complex, which covalently bonds the blue light-absorbing naphthalimide derivative to the BODIPY moiety. In some embodiments, the linker complex may include a single bond between the naphthalimide derivative and the BODIPY moiety.

[0067] In some embodiments, the linker complex may include a substituted ester, an unsubstituted ester, a substituted ether, or an unsubstituted ether. In some embodiments, the linker complex may include optionally substituted ester groups.

[0068] In some embodiments, the linker complex includes a substituted ester group, and the linker complex has the following structure:

Chem.

[0069] In some embodiments, the linker complex may include an unsubstituted ester group, and the linker complex has the following structure:

Chem.

[0070] In some embodiments, the linker complex may be: [[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ [ka] It is possible.

[0076] In some embodiments, the linker complex may be -O(CH2)6-.

[0077] In some embodiments, the linker composite is [ka] It is possible.

[0078] In some embodiments, the linker composite is [ka] It is possible.

[0079] In some embodiments, the linker composite is [ka] It is possible.

[0080] In some embodiments, the linker composite is [ka] It is possible.

[0081] In some embodiments, the linker composite is [ka] It is possible.

[0082] In some embodiments, the linker composite is [ka] It is possible.

[0083] In some embodiments, the linker complex is

Chemical formula

[0084] In some embodiments, the linker complex is

Chemical formula

[0085] In some embodiments, the linker complex is

Chemical formula

[0086] In some embodiments, the linker complex is

Chemical formula

[0087] In some embodiments, the linker complex is

Chemical formula

[0088] In some embodiments, the linker complex is

Chemical formula

[0089] In some embodiments, the linker complex is

Chemical formula

[0090] In some embodiments, the linker complex can be -O(CH2)6-.

[0091] In some embodiments, the linker composite is [ka] It is possible.

[0092] The photoluminescent complexes of this disclosure may include a BODIPY moiety.

[0093] The BODIPY part is given by the following general formula: [ka] (In the formula, R 1 and R 6 This can be independently selected from hydrogen (H), saturated or unsaturated alkyl groups, such as methyl groups and / or alkene groups. R 3 and R 4 These can be independently selected from C1-C2 alkyl groups, for example, methyl groups. R 2 and R 5 This can be independently selected from hydrogen (H), saturated alkyl, unsaturated alkyl, cyano(-CN), alkyl esters (e.g., ethyl ester, 2-ethylhexyl ester, 2,2,2-trifluoroethyl ester, glycol ester), or aryl esters (e.g., benzyl ester (-COOCH2Ph)). R 7 and R 8 This can be independently selected from hydrogen (H), C1-C3 alkyl (e.g., methyl (-CH3)), halide (e.g., F or Cl), and / or C1-C3 alkoxy (e.g., methoxy (-OCH3)). L may have (which can represent a linker complex containing an optionally substituted ester or an optionally substituted ether linker).

[0094] In some embodiments, the BODIPY portion of the present disclosure is R 1 , R3 , R 4 and R 6 Each of them is methyl, and R 2 and R 5 The substituted ester group may be a substituted ester group, and the substituted ester group contains a C1-C7 alkyl chain or a polyglycol chain, R 7 and R 8 Each of these is methyl, and L may be a BODIPY moiety containing a linker complex.

[0095] In some embodiments, R 2 and R 5 Independently, [ka] That's fine.

[0096] In some embodiments, R 2 teeth, [ka] That is the case.

[0097] In some embodiments, R 2 teeth, [ka] That is the case.

[0098] In some embodiments, R 2 teeth, [ka] That is the case.

[0099] In some embodiments, R 2 teeth, [ka] That is the case.

[0100] In some embodiments, R 2teeth, [ka] That is the case.

[0101] In some embodiments, R 5 teeth, [ka] That is the case.

[0102] In some embodiments, R 5 teeth, [ka] That is the case.

[0103] In some embodiments, R 5 teeth, [ka] That is the case.

[0104] In some embodiments, R 5 teeth, [ka] That is the case.

[0105] In some embodiments, R 5 teeth, [ka] That is the case.

[0106] The photoluminescent complexes of this disclosure can be represented by the following, which are provided for illustrative purposes only and not to be construed as limiting: [ka] [ka]

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[0107] Some embodiments include a photoluminescent complex, which comprises a blue light-absorbing xanthenoizoquinoline derivative. The blue light-absorbing xanthenoizoquinoline derivative may include an organic lumiphore. In some embodiments, the xanthenoizoquinoline derivative may have maximum absorption at any wavelength of light within the range of 400 nm to about 480 nm, about 400 nm to about 410 nm, about 410 nm to about 420 nm, about 420 nm to about 430 nm, about 430 nm to about 440 nm, about 440 nm to about 450 nm, about 450 nm to about 460 nm, about 460 nm to about 470 nm, about 470 nm to about 480 nm, or any wavelength limited by any of these values. In some embodiments, the photoluminescent complex may have an absorption maximum peak at about 450 nm. In other embodiments, the blue light-absorbing xanthenoisoquinoline derivative may have a maximum peak absorption of approximately 405 nm. In yet another embodiment, the blue light-absorbing xanthenoisoquinoline derivative may have a maximum peak absorption of approximately 480 nm.

[0108] Some embodiments include a photoluminescent complex, which includes a blue light-absorbing naphthalimide derivative. The blue light-absorbing naphthalimide derivative may include an organic luminiphore. In some embodiments, the naphthalimide derivative may have maximum absorption at any wavelength of light within the range of 400 nm to about 480 nm, about 400 nm to about 410 nm, about 410 nm to about 420 nm, about 420 nm to about 430 nm, about 430 nm to about 440 nm, about 440 nm to about 450 nm, about 450 nm to about 460 nm, about 460 nm to about 470 nm, about 470 nm to about 480 nm, or any wavelength limited by any of these values. In some embodiments, the photoluminescent complex may have an absorption maximum peak at about 450 nm. In other embodiments, the blue light-absorbing naphthalimide derivative may have a maximum peak absorption at about 405 nm. In yet another embodiment, the blue light-absorbing naphthalimide derivative may have a maximum peak absorption of approximately 480 nm.

[0109] Some embodiments include a color conversion film, which comprises a color conversion layer including a resin matrix and a photoluminescent complex dispersed within the resin matrix. In some embodiments, the color conversion film may include one or more complexes described herein.

[0110] Some embodiments include a color conversion film which may have a thickness of about 1 μm to about 200 μm. In some embodiments, the color conversion film has a thickness of about 1 μm to about 5 μm, about 5 μm to about 10 μm, about 10 μm to about 15 μm, about 15 μm to about 20 μm, about 20 μm to about 40 μm, about 40 μm to about 80 μm, about 80 μm to about 120 μm, about 120 μm to about 160 μm, about 160 μm to about 200 μm, or any thickness within a range limited by any of the above values.

[0111] In some embodiments, the color conversion film can absorb light in the wavelength range of approximately 400 nm to approximately 480 nm and emit light in the wavelength range of approximately 500 nm to approximately 560 nm.

[0112] In some embodiments, the color conversion film may further include a transparent substrate layer. The transparent substrate layer has two opposing surfaces, where the color conversion layer is positioned on the surface of the transparent layer adjacent to the light source and may be in physical contact with it. The transparent substrate is not particularly limited, and those skilled in the art can select a transparent substrate from those used in the art. Some non-limiting examples of transparent substrates include PE (polyethylene), PP (polypropylene), PEN (polyethylene naphthalate), PC (polycarbonate), PMA (polymethyl acrylate), PMMA (polymethyl methacrylate), CAB (cellulose acetate butyrate), PVC (polyvinyl chloride), PET (polyethylene terephthalate), PETG (glycol-modified polyethylene terephthalate), PDMS (polydimethylsiloxane), COC (cycloolefin copolymer), PGA (polyglycolide or polyglycolic acid), PLA (polylactic acid), PCL (polycaprolactone), PEA (polyethylene adipate), PHA (polyhydroxyalkanoate), PHBV (poly(3-hydroxybutyrate-co-3-hydroxyvalerate)), PBE (polybutylene terephthalate), and PTT (polytrimethylene terephthalate). Any of the above can be used individually or in combination to form a transparent substrate layer.

[0113] In some embodiments, the transparent substrate may have two opposing surfaces. In some embodiments, the color-converting film may be placed on one of the opposing surfaces and be in physical contact with it. In some embodiments, the surface of the transparent substrate on which the color-converting film is not placed may be adjacent to a light source. In some examples, the substrate may function as a support during the fabrication of the color-converting film. The type of substrate used is not particularly limited, and the material and / or thickness is not limited as long as it is transparent and can function as a support. Those skilled in the art will be able to determine what material and thickness should be used as the support substrate.

[0114] Some embodiments include a method for producing a color-converting film, which comprises dissolving a photoluminescent compound and a binder resin described herein in a solvent and applying the mixture to the surface of a transparent substrate.

[0115] Examples of binder resins that can be used with photoluminescent complexes (sometimes multiple complexes) include acrylic resins, polycarbonate resins, ethylene-vinyl alcohol copolymer resins, ethylene-vinyl acetate copolymer resins and their saponification products, AS resins, polyester resins, vinyl chloride-vinyl acetate copolymer resins, polyvinyl butyral resins, polyvinylphosphonic acid (PVPA), polystyrene resins, phenolic resins, phenoxy resins, polysulfones, nylon, cellulose resins, and cellulose acetate resins. In some embodiments, the binder resin may be a polyester resin and / or an acrylic resin.

[0116] In some embodiments, solvents that can be used to dissolve or disperse complexes and resins include alkanes, e.g., butane, pentane, hexane, heptane, and octane; cycloalkanes, e.g., cyclopentane, cyclohexane, cycloheptane, and cyclooctane; alcohols, e.g., ethanol, propanol, butanol, amyl alcohol, hexanol, heptanol, octanol, decanol, undecanol, diacetone alcohol, and furfuryl alcohol; Cellosolves®, e.g., Methyl Cellosolve®, Ethyl Cellosolve®, Butyl Cellosolve®, Methyl Cellosolve® acetate, and Ethyl Cellosolve® acetate, propylene glycol and its derivatives, such as propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monobutyl ether acetate, and dipropylene glycol dimethyl ether, ketones such as acetone, methyl amyl ketone, cyclohexanone, and acetophenone, ethers such as dioxane and tetrahydrof Examples of solvents include lanes, esters such as butyl acetate, amyl acetate, ethyl butyrate, butyl butyrate, diethyl oxalate, ethyl pyruvate, ethyl 2-hydroxybutyrate, ethyl acetacetate, methyl lactate, ethyl lactate, and methyl 3-methoxypropionate, halogenated hydrocarbons such as chloroform, methylene chloride, and tetrachloroethane, aromatic hydrocarbons such as benzene, toluene, xylene, and cresol, and / or highly polar solvents such as dimethylformamide, dimethylacetamide, and N-methylpyrrolidone.

[0117] Some embodiments include a backlight unit, which may comprise the aforementioned color conversion film.

[0118] Other embodiments include display devices that may include a backlight unit as described herein.

[0119] Unless otherwise specified, all figures used herein and in the embodiments to describe properties such as the amount of components, molecular weight, and reaction conditions should be understood in all cases to be modified by the term "approximately." Therefore, unless otherwise specified, the numerical parameters shown herein and in the accompanying embodiments are approximations that may vary depending on the desired properties to be obtained, at least not as an attempt to limit the application of the doctrine of equivalents. Within the scope of the embodiments, each numerical parameter should be interpreted at least by applying common rounding techniques in light of the reported number of significant figures.

[0120] With respect to the disclosed processes and / or methods, the functions performed in the processes and methods may be implemented in various orders, as may be indicated by the context. Furthermore, the outlined steps and operations are presented as examples only, and some steps and operations may be optional, combined into fewer steps and operations, or extended into additional steps and operations.

[0121] This disclosure may occasionally describe different components that are contained within or related to other different components. Such represented configurations are merely illustrative, and many other configurations can be realized to achieve the same or similar functions.

[0122] In general, the terms used in this disclosure and the accompanying embodiments (e.g., the text of the accompanying embodiments) are intended to be “open” terms (for example, the term “including” should be interpreted as “including, but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes, but not limited to,” etc.). Furthermore, where a specific number of elements are introduced, this can be interpreted as meaning at least the number stated, as may be indicated by the context (for example, the literal statement of “two statements” without other modifiers means at least two statements of two or more statements). Any disjunctions and / or disjunctions that, when used in this disclosure, represent two or more alternative terms should be understood to construed as construing the possibility of including one of the terms, either of the terms, or both of the terms. For example, the phrase "A or B" would be understood to include the possibilities of "A" or "B" or "A and B".

[0123] In the context describing this disclosure (particularly in the context of the embodiments described below), the terms “singular ("a", “an", “the")” and similar reference subjects should be construed to include both singular and plural forms unless otherwise specifically indicated herein or unless the context clearly contradicts this interpretation. The use of any examples or representative phrases provided herein (e.g., “such as”) is intended solely to better illustrate this disclosure and does not imply any limitation on the scope of any embodiment. The language herein should not be construed to represent any unexpressed elements essential to the implementation of this disclosure.

[0124] The grouping of alternative elements or embodiments disclosed herein should not be construed as limiting. Members of each group may be referenced and embodied individually or in any combination with other members of the group or other elements found herein. For convenience and / or patentability reasons, it is anticipated that one or more members of a group may be included in or removed from a group. If such inclusion or removal occurs, this specification will include the modified groups and will therefore satisfy the description of all Markush groups used in the accompanying embodiments.

[0125] Certain embodiments include the best mode known to the inventors for carrying out the Disclosure. Naturally, variations of these embodiments will be apparent to those skilled in the art by reading the above description. The inventors anticipate that those skilled in the art will use such variations as needed, and they intend that the Disclosure will be carried out in ways other than those specifically described herein. Thus, embodiments include all variations and equivalents of the subject matter described in the embodiments, as permitted by applicable law. Furthermore, unless otherwise specifically indicated herein, or unless it is clearly inconsistent with the context, all combinations of the above elements in all possible variations are contemplated. Finally, it should be understood that the embodiments disclosed herein are illustrative of the principles of the embodiments. Other variations that may be used are within the scope of the embodiments. Thus, alternative embodiments may be used, for example, in accordance with the teachings herein, but not limited thereto. Thus, embodiments are not limited to those strictly shown and described.

[0126] Embodiment Embodiment 1: A photoluminescent complex, The blue light absorbing portion, Linker complex and The boron-dipyromethene (BODIPY) part, Includes, A photoluminescent complex in which the linker complex covalently bonds the blue light absorbing portion and the BODIPY portion, the blue light absorbing portion absorbs light energy of a first excitation wavelength and transfers the energy to the BODIPY portion, the BODIPY portion absorbs the energy from the blue light absorbing portion and emits light energy of a second, higher wavelength, and the photoluminescent complex has an emission quantum yield of more than 80%.

[0127] Embodiment 2: The photoluminescent complex of Embodiment 1, wherein the blue light absorbing portion is a xanthenoisoquinoline derivative.

[0128] Embodiment 3 The xanthenoizoquinoline derivative has the general formula: [ka] (In the formula, R 0 The photoluminescent complex of Embodiment 2 is independently selected from hydrogen (H), C1-C3 alkyl, optionally substituted aryl, or optionally substituted heteroaryl.

[0129] Embodiment 4: The photoluminescent complex of Embodiment 1, wherein the blue light absorbing portion is a naphthalimide derivative.

[0130] Embodiment 5 The naphthalimide derivative is of the general formula: [ka] (In the formula, R 0 These are independently hydrogen (H), substituted or unsubstituted aryl, -CF3, 3,5-bis(trifluoromethyl)phenyl [ka] ) selected from or R 0 There are no substituents, and X is independently selected from oxygen (O) or sulfur (S), and R 1These are independently hydrogen (H), substituted or unsubstituted aryl, C1-C5 alkyl, phenyl, 3,5-bis(trifluoromethyl)phenyl ( [ka] ), 4-(trifluoromethyl)phenyl( [ka] ), 4-(tert-butyl)phenyl ( [ka] ), 4-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl( [ka] ) selected from or R 1 The photoluminescent complex of Embodiment 4, which has no substitutions.

[0131] Embodiment 6 The BODIPY portion is a general formula: [ka] (In the formula, R 1 and R 6 R is independently selected from hydrogen (H), saturated or unsaturated alkyl groups, or alkene groups. 3 and R 4 R is independently selected from C1-C2 alkyl groups. 2 and R 5 R is independently selected from hydrogen (H), saturated alkyl, unsaturated alkyl, cyano (-CN), alkyl ester (-COOCH2CH3), aryl ester (-COOCH2Ar), or EtO2C. 7 and R 8 The photoluminescent complex of Embodiment 1, wherein is independently selected from hydrogen (H), a methyl group, a halide, or a C1-C3 alkoxy.

[0132] Embodiment 7 R 1 , R 3 , R 4 and R 6 However, independently, selected from C1-C3 alkyl or methyl groups, R 2 and R 5 However, independently selected from C1-C3 ester groups or CH3CH2CO2 esters, R 7 and R 8 However, independently selected from methyl groups, the photoluminescent complex of Embodiment 6.

[0133] Embodiment 8 The BODIPY portion has the following structure: [ka] A photoluminescent complex of Embodiment 1, comprising the above.

[0134] Embodiment 9 The BODIPY portion has the following structure: [ka] A photoluminescent complex of Embodiment 1, comprising the above.

[0135] Embodiment 10: The photoluminescent complex of Embodiment 6, wherein L is a linker complex that may be a substituted ester, an unsubstituted ester, a substituted ether, or an unsubstituted ether.

[0136] Embodiment 11 The unsubstituted ester has the following structure: [ka] A photoluminescent complex of Embodiment 10, including one of the above.

[0137] Embodiment 12 The substituted ester has the following structure: [ka] A photoluminescent complex of Embodiment 10, including one of the above.

[0138] Embodiment 13 The unsubstituted and / or substituted ether has the following structure: [ka] A photoluminescent complex of Embodiment 10, including one of the above.

[0139] Embodiment 14 The photoluminescent complex has the following structure: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] A photoluminescent complex of Embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13, comprising one of the above.

[0140] Embodiment 15 A color conversion film, A transparent substrate layer, A color conversion layer containing a resin matrix, A photoluminescent complex comprising a photoluminescent complex in which the photoluminescent compound is dispersed in the resin matrix, as in the photoluminescent complex of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14, and Color conversion film, including

[0141] Embodiment 16: A color conversion film of Embodiment 15, further comprising a singlet oxygen quenching agent.

[0142] Embodiment 17 A color conversion film of Embodiment 15, further comprising a free radical scavenger.

[0143] Embodiment 18: The color conversion film of Embodiment 15, wherein the color conversion film has a thickness between 10 μm and 200 μm.

[0144] Embodiment 19: The color conversion film of Embodiment 15, wherein the color conversion film absorbs light in the wavelength range of approximately 400 nm to approximately 480 nm and emits light in the wavelength range of 500 nm to approximately 560 nm.

[0145] Embodiment 20 A method for producing the color conversion film of Embodiments 15, 16, 17, 18 or 19, Dissolving the photoluminescent complex and binder resin of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 in a solvent, A method comprising applying the mixture to one of the opposing surfaces of a transparent substrate.

[0146] Embodiment 21 A backlight unit comprising the color conversion film of Embodiment 15, 16, 17, 18, or 19.

[0147] Embodiment 22 A display device including the backlight unit of Embodiment 21. [Examples]

[0148] The embodiments of the photoluminescent complexes described herein have been found to have improved performance compared to other forms of dyes used in color conversion films. These advantages are further demonstrated by the following examples, which are intended solely to illustrate the disclosure and are not intended to limit the scope or fundamental principles in any way.

[0149] Example 1.1 Comparative example 1 (CE-1): [ka]

[0150] CE-1: 0.75 g of 4-hydroxyl-2,6-dimethylbenzaldehyde (5 mmol) and 1.04 g of 2,4-dimethylpyrrole (11 mmol) were dissolved in 100 mL of anhydrous dichloromethane. The solution was degassed for 30 minutes. Next, one drop of trifluoroacetic acid was added. The solution was stirred overnight at room temperature under an argon atmosphere. DDQ (2.0 g) was added to the resulting solution, and the mixture was stirred overnight. The next day, the solution was filtered and washed with dichloromethane to obtain dipyrrolemethane (1.9 g). Next, 1.0 g of dipyrrolemethane was dissolved in 60 mL of THF. 5 mL of trimethylamine was added to the solution, and it was degassed for 10 minutes. After degassing, 5 mL of trifluoroboron-diethyl ether was slowly added, and the mixture was subsequently heated at 70°C for 30 minutes. The resulting solution was loaded onto silica gel and purified by flash chromatography using dichloromethane as the eluent. The desired fraction was collected and dried under reduced pressure to obtain 0.9 g of an orange solid (76% yield). LCMS(APCI+):C 21 H 24 Calculated value for BF2N2O: (M+H) = 369; measured value: 369. 1 ¹H NMR (400 MHz, chloroform-d) δ 6.64 (s, 2H), 5.97 (s, 2H), 4.73 (s, 1H), 2.56 (s, 6H), 2.09 (s, 6H), 1.43 (s, 6H).

[0151] Example 1.2 Comparative Example 2 (CE-2) was synthesized as described in Wakamiya, Atsushi et al. Chemistry Letters, 37(10), 1094-1095; 2008.

[0152] Example 2: Synthesis of photoluminescent complexes (PLCs) Synthesis of PLC-1 [ka]

[0153] Compound PLC-1.1 [ka]

[0154] Step 1: A mixture of ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (1.0 g, 6.0 mmol), 4-hydroxy-2,6-dimethylbenzaldehyde (0.449 g, 3.0 mmol), and tosylic acid (50 mg, 0.29 mmol) in 50 mL of 1,2-dichloroethane was degassed and stirred overnight at room temperature. LCMS analysis showed one major peak with m / e+ = 467.

[0155] Step 2: DDQ (0.817 g, 3.6 mmol) was added to the obtained solution, and the mixture was stirred at room temperature for 30 minutes. LC-MS analysis showed that all starting materials were converted to the desired product with m / e+=465.

[0156] Procedure 3: While cooling in an ice bath, 1.7 mL of triethylamine and 2.2 mL of BF3 - diethyl ether were sequentially added to the mixture from Procedure 2. The whole was heated at 50 °C for 1 hour. LCMS analysis showed about 30% conversion. To this mixture, an additional 1 mL of triethylamine and 1 mL of BF3 - diethyl ether were added, and the whole was heated at 50 °C for an additional 1 hour. LCMS analysis showed that all starting materials were converted to the desired BODIPY product with m / e + = 513 and m / e - = 512. The reaction mixture was directly subjected to silica gel and purified by flash chromatography using a hexane / ethyl acetate (0% → 30% ethyl acetate) eluent. The main desired peak was collected, and removal of the solvent gave an orange solid (1.0 g, 65% yield). LCMS (APCI): C 27 H 32 Calculated value (M + H) for BF2N2O5: 513.2; Measured value: 513. 1H NMR (400 MHz, chloroform - d) δ 7.26 (s, 3H), 6.68 (s, 2H), 4.29 (q, J = 7.1 Hz, 4H), 2.84 (s, 6H), 2.05 (s, 6H), 1.34 (t, J = 7.1 Hz, 6H).

[0157] Compound PLC - 1.2

Chemical Structure

[0158] A mixture of 2-nitrophenol (6.6 g, 48 mmol) and KOH powder (2.4 g, 43 mmol) was mixed and stirred under vacuum for 30 minutes. Then copper powder (0.4 g) was added, followed by 100 mL of anhydrous DMF. The mixture was stirred for 5 minutes, then 4-chloronaphthalic anhydride (5.1 g, 22 mmol) was added. The mixture was degassed and then heated under reflux for 1.5 hours. After cooling to room temperature, 100 mL of 20% hydrochloric acid was added dropwise to the resulting reaction mixture and allowed to stand for 2 hours. The precipitate was collected by filtration and then dried overnight under vacuum to obtain a yellowish-brown solid (4.6 g). This was further purified by stirring in reflux acetic acid (50 mL) for 2 hours and then cooling to room temperature. After filtration and drying in air, a yellow solid (3.0 g, 41% yield) was obtained. Confirmed by LC-MS (APCI): C 18 H 10 Calculated value (M+H) for NO6: 336.0; measured value: 336. 1H NMR (400MHz, chloroform-d) δ 8.80 (dd, J=8.5, 1.2Hz, 1H), 8.72 (dd, J=7.3, 1.2Hz, 1H), 8.50 (d, J=8.2Hz, 1H), 8.19 (dd, J=8.2, 1.7Hz, 1H), 7.90 (dd, J=8.5, 7.3Hz, 1H), 7.79 (td, J=7.9, 1.7Hz, 1H), 7.54 (td, J=8.0, 1.3Hz, 1H), 7.39 (dd, J=8.3, 1.2Hz, 1H), 6.89 (d, J=8.2Hz, 1H).

[0159] Compound PLC-1.3 [ka]

[0160] A mixture of 4-(2-nitrophenoxyl)-1,8-naphthalic anhydride (2.0 g, 6 mmol) and iron powder (less than 10 μm, 0.91 g, 16 mmol) in acetic acid (75 mL) was heated under reflux for 30 minutes. The resulting solution was poured into water (220 mL). The resulting precipitate was collected by filtration, washed with water, completely dried in air, and then dried under vacuum to obtain a yellow solid (1.65 g, 90% yield). Confirmed by LC-MS (APCI): C 18 H 12 Calculated value (M+H) for NO4: 306.1; Measured value: 306.

[0161] Compound PLC-1.4 [ka]

[0162] Compound 4-(2-aminophenoxy)-1,8-naphthalic anhydride (1.5 g, 4.9 mmol) was dispersed in acetic acid (35 mL) and cooled to 0°C. While stirring, pre-cooled hydrochloric acid (3 mL, 37 mmol) was added, and then sodium nitrite solution in 12 mL of water (3.29 g, 46 mmol) was added dropwise at 0°C. The mixture was stirred at 0°C for 1 hour, then transferred to an additional funnel, and refluxed copper sulfate solution (5.08 g, 20 mmol in 50 mL of water) was added dropwise over 1 hour. After cooling to room temperature, the precipitate was collected by filtration, washed with water, and then dried in air and then under vacuum to obtain a yellow solid (0.92 g, 65% yield). Confirmed by LC-MS (APCI):C 18 Calculated value (M-) for H8O4: 288.0; measured value: 288. 1H NMR (400MHz, chloroform-d) δ 8.61 (dd, J=17.1, 8.1Hz, 2H), 8.09 (d, J=8.0Hz, 1H), 7.97 (d, J=7.9Hz, 1H), 7.59 (t, J=7.7Hz, 1H), 7.40 (t, J=8.1Hz, 2H), 7.33 (d, J=8.4Hz, 1H).

[0163] Compound PLC-1.5 [ka]

[0164] A mixture of 1H,3H-isochromeno[6,5,4-mna]xanthene-1,3-dione (100 mg, 0.347 mmol) and 2-(4-aminophenyl)acetic acid (135 mg, 0.9 mmol) in 5 mL of DMF was heated in a microwave reactor at 165 °C for 2 h. After cooling to 50 °C, 1.5 mL of acetone was added dropwise to the resulting solution to form a yellow precipitate, which was collected by filtration, washed with acetone, and dried in air to give a yellow solid (88 mg, 61% yield). Confirmed by LCMS (APCI): C 26 H 15 Calculated for C H NO5 (M-): 421.1; Found: 421. 1H NMR (400 MHz, DMSO-d6) δ 8.27 (d, J = 45.1 Hz, 4H), 7.67 - 7.00 (m, 8H), 3.58 (s, 2H).

[0165] Compound PLC-1

Chemical formula

[0166] A mixture of compound PLC-1.5 (36 mg, 0.086 mmol), compound PLC-1.1 (40 mg, 0.078 mmol), DMAP / TsOH salt (59 mg, 0.2 mmol) and DIC (0.1 mL, 0.63 mmol) in 5 mL of DCM was stirred at room temperature overnight and then at 45 °C for 2 h. The resulting mixture was subjected to silica gel and purified by flash chromatography using an eluent of DCM / ethyl acetate (0% → 10% ethyl acetate). The desired product peak was collected and concentrated under reduced pressure. The resulting solid was further washed with methanol and dried in air to give an orange solid (38 mg, 53% yield). Confirmed by LCMS (APCI): C 53 H 44Calculated value (M-) for BF2N3O9: 915.3; Measured value: 915. 1H NMR (400MHz) δ 8.55(dd,J=18.8,8.1Hz,2H), 8.04(d,J=7.7Hz,1H), 7.93(d,J=8.0Hz,1H), 7.52(dd,J=19.7,8.0Hz,3H), 7.40~7.23(m,5H), 6.96(s,2H) ), 4.19(q,J=7.1Hz,4H), 3.92(s,2H), 3.37(s,1H), 2.75(s,6H), 2.54(d,J=3.3Hz,1H), 2.06(s,6H), 1.64(s,6H), 1.25(t,J=7.1Hz,6H).

[0167] Synthesis of PLC-2 [ka]

[0168] Compound PLC-2.1 [ka]

[0169] A mixture of 1H,3H-isochromeno[6,5,4-mna]xanthene-1,3-dione (100 mg, 0.347 mmol) and 4-(4-aminophenyl)butanoic acid (125 mg, 0.7 mmol) in 5 mL of DMF was heated in a microwave reactor at 165°C for 2.5 hours. 15 mL of acetone was added to this mixture, and the resulting precipitate was collected by filtration and dried in air to obtain a yellow solid (120 mg, 77% yield). Confirmed by LC-MS (APCI):C 28 H 19 Calculated value for NO5 (M-): 449.1; measured value: 449. 1H NMR (400MHz, DMSO-d6) δ 8.38 (d, J=41.6Hz, 4H), 7.81~6.97 (m, 8H), 2.69~2.64 (m, 2H), 2.26 (t, J=7.2Hz, 2H), 1.87 (p, J=7.2Hz, 2H).

[0170] Compound PLC-2 [ka]

[0171] A mixture of compound PLC-1.5 (45 mg, 0.1 mmol), compound PLC-1.1 (40 mg, 0.078 mmol), DMAP / TsOH salt (59 mg, 0.2 mmol), and DIC (0.1 mL, 0.63 mmol) in 5 mL of DCM was stirred overnight at room temperature, and then stirred at 45 °C for 2 hours. The reaction mixture was passed over silica gel and purified by flash chromatography using DCM / ethyl acetate (0% → 10% ethyl acetate) as the eluent. The desired product peak was collected and concentrated under reduced pressure. The resulting solid was further washed with methanol and dried in air to obtain an orange solid (46 mg, 62% yield). Confirmed by LC-MS (APCI):C 55 H 49 Calculated value for BF2N3O9 (M+H): 944.3; Actual value: 944. 1H NMR (400MHz,) δ 8.54(dd,J=18.7,8.1Hz,2H), 7.40~7.25(m,5H), 7.20(d,J=8.3Hz,2H), 6.93(s,2H), 4.19(q,J=7.1Hz,4H), 2.80(t,J= 7.6Hz,2H), 2.75(s,6H), 2.62(t,J=7.4Hz,2H), 2.10(t,J=7.6Hz,2H), 2.06(s,6H), 1.65(s,6H), 1.25(t,J=7.1Hz,6H).

[0172] Synthesis of PLC-3 [ka]

[0173] Compound PLC-3.1 [ka]

[0174] A mixture of 4-bromo-1,8-naphthalic anhydride (2.77 g, 10 mmol) and 4-bromo-2-nitrophenol (3.27 g, 15 mmol) was degassed under vacuum for 30 minutes, then anhydrous NMP (50 mL) was added, followed by sodium hydroxide (0.2 g, 5 mmol) and copper powder (0.318 g, 5 mmol). The mixture was sprayed with argon for 20 minutes, and then heated overnight at 180 °C under an argon atmosphere. After cooling to room temperature, 50 mL of 20% hydrochloric acid aqueous solution was added dropwise to the solution, followed by 50 mL of water. The resulting mixture was left to stand for 3 hours, then filtered to collect the precipitate, which was dried under vacuum to obtain 4.6 g of crude product. The crude product was dispersed in 30 mL of acetone and stirred overnight at room temperature to dissolve impurities. After filtration and drying under vacuum, a yellowish-brown solid (3.3 g, 80% yield) was obtained as the desired product. LC-MS(APCI+):C 18 Calculated value (M+H) for H9BrNO6: 413.95; measured value: 414. 1H NMR (400MHz, TCE-d2) δ: 8.70 (dd, J=8.4, 1.2Hz, 1H), 8.63 (dd, J=7.3, 1.2Hz, 1H), 8.41 (d, J=8.3Hz, 1H), 8.24 (d, J=2.4Hz, 1H), 7.89~7.79 (m, 2H), 7.20 (d, J=8.7Hz, 1H), 6.82 (d, J=8.3Hz, 1H).

[0175] Compound PLC-3.2 [ka]

[0176] A mixture of compound PLC-3.1 (1.5 g, 3.6 mmol) and iron powder (0.60 g, 10.8 mmol) in acetic acid (50 mL) was heated at 125°C for 30 minutes. After cooling to room temperature, 100 mL of water was added to the mixture while stirring. The resulting mixture was filtered, washed with water, and dried in air and under vacuum to obtain a solid (1.35 g, 82% yield). LCMS(APCI-):C 18 H 10Calculated value for BrNO4: 382.98; measured value: 383. 1H NMR (400MHz, DMSO-d6) δ: 9.01~8.26 (m, 3H), 7.96 (s, 1H), 6.93 (dd, J=85.2, 36.5Hz, 4H), 5.54 (s, 2H).

[0177] Compound PLC-3.3 [ka]

[0178] PLC-3.2 (2.65 g, 6.9 mmol) was dispersed in acetic acid (50 mL) / water (10 mL) and cooled to 0°C. While stirring, pre-cooled hydrochloric acid (2.8 mL, 34.5 mmol) was added, followed by the dropwise addition of sodium nitrite solution (3.57 g, 52 mmol) in 15 mL of water at 0°C. After stirring the entire mixture at 0°C for 1 hour, it was transferred to an additional funnel and added dropwise to copper sulfate solution (12 g, 47 mmol, in 140 mL of water) at 130°C for 1 hour. After cooling to room temperature, the precipitate was collected by filtration, washed with water (100 mL x 3), and then stirred in 50 mL of acetone at 40°C for 30 minutes. Filtered and dried in air, then under vacuum, to obtain a yellowish-brown solid (1.76 g, 70% yield). LCMS(APCI+):C 18 Calculated value (M+H) for H8BrO4: 366.95; measured value: 367. 1H NMR (400MHz, d2-TCE) δ: 8.51 (dd, J=12.3, 8.1Hz, 2H), 8.12 (d, J=2.3Hz, 1H), 7.86 (d, J=7.9Hz, 1H), 7.60 (dd, J=8.8, 2.3Hz, 1H), 7.28 (d, J=8.3Hz, 1H), 7.23 (d, J=8.8Hz, 1H).

[0179] Compound PLC-3.4 [ka]

[0180] A mixture of PLC-3.3 (400.0 mg, 1.1 mmol), 4-aminophenylacetic acid (329.4 mg, 2.2 mmol), and DMAP (9.3 mg, 0.080 mmol) in DMF (8 mL) was degassed at room temperature. The mixture was then heated to 165°C and held at this temperature for 3 hours. TLC and LC-MS showed approximately 95% conversion without observable side reactions. The mixture was cooled to 50°C. It was then poured into an acetone solution (40 mL) and pre-cooled in an ice bath. The mixture was held at 0°C for 2 hours and then stirred overnight at room temperature. The solid was collected by vacuum filtration and washed with acetone (4 mL). It was then dried in a vacuum oven at 100°C for 3 hours to obtain pure compound PLC-3.4 as a yellowish-brown solid (395.0 mg, 73% yield). MS(APCI):C 26 H 14 Calculated value for BrNO5 ([M+H]+) = 500; measured value: 500. 1H NMR (400MHz, CDCl2CDCl2) δ 8.65 (d, J=8.0Hz, 1H), 8.62 (d, J=8.0Hz, 1H), 8.21 (dd, J=6.4Hz, 2.4Hz, 1H), 7.99 (bs, 1H), 7.95 (t, J=7.6Hz, 1H), 7.67 (dd, J=8.4Hz, 2.4Hz, 1H), 7.53 (d, J=8.0Hz, 2H), 7.37 (d, J=8.4Hz, 1H), 7.32 (m, 3H), 2.94 (s, 2H).

[0181] Compound PLC-3.5 [ka]

[0182] A mixture of compound PLC-3.4 (400.0 mg, 0.80 mmol), 4-(trifluoromethyl)phenylboronic acid (262.2 mg, 1.6 mmol), Pd(dppf)Cl2 (41.0 mg, 0.056 mmol), and K2CO3 (298.0 mg, 2.2 mmol) in THF / DMF / H2O (22 ml / 4.4 ml / 2.2 ml) was degassed at room temperature. The reaction mixture was heated to 80°C and the reaction was maintained at this temperature overnight. The reaction was monitored using TLC. After completion, the reaction products were work-treated by adding 0.1 N HCl (150 ml) and SiO (150 ml). The aqueous phase was further extracted with THF (150 ml x 3). The combined organic phases were dried over anhydrous Na2SO4, concentrated under a rotary evaporator (rotavapor), and purified by flash chromatography using DCM in toluene (0% → 40%, containing 0.1% TFA) as an eluent to obtain pure RL-naphthalimide derivative PLC-3.5 as a yellow / yellowish-brown solid (363.0 mg, 80% yield). MS(APCI):C 33 H 18 Calculated value for F3NO5 ([M+H]+) = 566; measured value: 566. 1H NMR (400MHz, DMSO-d6): 8.76 (m, 1H), 8.56 (m, 2H), 8.52 (dd, J=8.0Hz, J=3.2Hz, 1H), 8.15 (m, 2H), 8.06 (m, 1H), 7.94 (d, J=8.0Hz, 2H), 7.66 (dd, J=8.0Hz, J=4.0Hz, 1H), 7.53 (m, 1H), 7.45 (d, J=8.0Hz, 2H), 7.33 (d, J=8.0Hz, 2H), 3.72 (s, 2H).

[0183] Compound PLC-3 [ka]

[0184] A mixture of compound PLC-3.5 (50 mg, 0.089 mmol), compound PLC-3.6 (30 mg, 0.059 mmol), DMAP / TsOH salt (15 mg, 0.051 mmol), and EDC·HCl (60 mg, 0.31 mmol) in 5 mL of DCM was stirred overnight at room temperature. The reaction mixture was placed on silica gel and purified by flash chromatography using DCM / ethyl acetate (0% → 10% ethyl acetate) as the eluent. The desired product peak was collected and concentrated under reduced pressure. The resulting solid was reprecipitated with ethyl acetate / methanol and dried in air to obtain an orange solid (45 mg, 72%). LCMS(APCI-):C 60 H 47 Calculated value for BF5N3O9: 1059.33; Measured value: 1059. 1H NMR (400MHz, methylene chloride-d2) δ 8.73 (d,J=7.9Hz,1H), 8.66 (d,J=8.3Hz,1H), 8.39 (d,J=2.2Hz,1H), 8.17 (d,J=8.0Hz,1H), 7.86 (dt,J=11.4,8.4Hz,5H), 7.64 (d,J=8.3Hz,2H), 7.57 (d,J=8.6H) z,1H), 7.43(d,J=8.3Hz,1H), 7.41~7.35(m,2H), 7.09(s,2H), 4.30(q,J=7.1Hz, 4H), 4.05(s,2H), 2.84(s,6H), 2.18(s,6H), 1.77(s,6H), 1.36(t,J=7.1Hz,6H).

[0185] Synthesis of PLC-4 [ka]

[0186] Compound PLC-4.1 [ka]

[0187] A 1 L 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. The system was flushed with argon. 6-bromo-1H,3H-benzo[de]isochromen-1,3-dione (40.0 mmol, 11.084 g) and 4-(tert-butyl)-2-nitrophenol (60.0 mmol, 11.712 g) were added to the flask, followed by anhydrous NMP (150 mL). NaOH (20.0 mmol, 800 mg) and copper (powder) (20.0 mmol, 1271 mg) were added to the flask, followed by anhydrous NMP (25 mL). The flask was stirred under an argon atmosphere with the heat block set to 170°C. The reaction mixture was stirred at this temperature overnight. The reaction mixture was cooled to room temperature and treated with water (175 mL) and 1N HCl (44 mL). The reaction mixture was stirred for 30 minutes, then filtered and washed with water. The precipitate was transferred to a flask containing acetone / DCM, evaporated to dryness, and then azeotropically mixed with toluene. The crude product was dissolved in a small amount of DCM and treated with methanol (300 mL). Part of the DCM and methanol were removed by rotary evaporation using a hot water bath (80°C). Once all the DCM had been removed, the mixture was cooled to room temperature and the solid was filtered off. 8.180 g of a dark-colored powder (yield 52%) was obtained. MS(APCI):C 22 H 17 Calculated value (M+H) for NO6: 392; measured value: 392. 1H NMR (400MHz, tetrachloroethane-d2) δ: 8.82 (dd, J=8.4, 1.2Hz, 1H), 8.71 (dd, J=7.3, 1.2Hz, 1H), 8.49 (d, J=8.3Hz, 1H), 8.16 (d, J=2.4Hz, 1H), 7.91 (dd, J=8.4, 7.3Hz, 1H), 7.80 (dd, J=8.6, 2.4Hz, 1H), 7.34 (d, J=8.6Hz, 1H), 6.91 (d, J=8.3Hz, 1H), 1.43 (s, 9H).

[0188] Compound PLC-4.2 [ka]

[0189] A 250 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. The system was flushed with argon. Compound (6-(4-(tert-butyl)-2-nitrophenoxy)-1H,3H-benzo[de]isochromene-1,3-dione) (10.0 mmol, 3.914 g) and 2-MeTHF (70 mL) were added to the flask. While stirring at room temperature, HCl (100 mmol, 4.0 N, 25 mL) and SnCl2·2H2O (40.0 mmol, 9.024 g) were added in water. The reaction mixture was stirred for 30 minutes under an argon atmosphere with the heat block set to 90°C. The reaction mixture was cooled to 0°C and made basic with 2N NaOH aqueous solution to pH approximately 8 (pH paper). The solid was filtered off (slow filtration), and the resulting solid was washed with 2-MeTHF (8 × 100 mL). The filtrate was transferred to a separatory funnel, and the layers were separated. The organic layer was dried over MgSO4, filtered, and evaporated to dryness under vacuum. 3.743 g (quantitative yield) was obtained. It was used in the next step without further purification. MS(APCI):C 22 H 19 Calculated value for NO4 (M+H) = 362; measured value: 362. 1 ¹H NMR (400MHz, tetrachloroethane-d2) δ 8.88 (dd, J=8.4, 1.2Hz, 1H), 8.69 (dd, J=7.3, 1.2Hz, 1H), 8.48 (d, J=8.4Hz, 1H), 7.89 (dd, J=8.4, 7.3Hz, 1H), 7.03~6.93 (m, 3H), 6.88 (dd, J=8.4, 2.3Hz, 1H), 1.35 (s, 9H).

[0190] Compound PLC-4.3 [ka]

[0191] A stirring bar, NaNO2 (30.0 mmol, 2.070 g), and water (10 mL) were placed in a 40 mL vial. The vial was stirred in an ice bath at 0°C. A stirring bar and the compound (6-(2-amino-4-(tert-butyl)phenoxy)-1H,3H-benzo[de]isochromen-1,3-dione) (4.00 mmol, 1.446 g) were placed in a 100 mL round-bottom flask. Ice AcOH (30 mL) and concentrated HCl (20.0 mmol, 12.1 N, 1.65 mL) were added to the flask. The mixture was stirred at room temperature for several minutes, then placed in an ice bath and stirred for about 1 minute. The NaNO2 solution was added before the acetic acid began to freeze. The NaNO2 was added over about 10 minutes. The diazo solution was stirred at 0°C for 1 hour. A 250 mL 2N round-bottom flask with a large stirring bar was prepared while stirring the diazo solution. A finned condenser and a dropping funnel were attached to the flask. The flask was clamped at an off-center neck, and the dropping funnel was positioned at an off-center neck, so that the solution hit the top of the vortex during stirring. CuSO4·5H2O (27.4 mmol, 6.842 g) and water (80 mL) were added to this flask. About 15 minutes before the diazo solution was obtained, the copper solution was started to heat to 130°C. When the solution reached 130°C, the diazo solution was transferred to the dropping funnel and added dropwise while stirring at high speed for about 30 minutes. After the addition was complete, the solution was heated for a further 1-2 minutes and then cooled in a water bath at room temperature. The precipitate was filtered and washed with water. The precipitate was dried by suction, and then the crude precipitate was dissolved / suspended in DCM and evaporated to dryness on about 10 g of flash silica gel. Purification was performed by flash chromatography on silica gel (220 g, solids, equilibration 50% DCM / hexane, elution 50% DCM / hexane (2 CV) → 100% DCM (20 CV) → isocratic DCM (15 CV) → 0% Â / DCM (0 CV) → 1% Â / DCM (10 CV)). Product tail. The fraction containing the product was evaporated to dryness under vacuum. 528 mg (38% yield) was obtained. MS(APCI):C 22 H 16 Calculated value for O4 (M+H) = 345; measured value: 345. 1¹H NMR (400MHz, tetrachloroethane-d2) δ 8.61 (d,J=7.9Hz,1H), 8.56 (d,J=8.4Hz,1H), 8.05 (d,J=2.2Hz,1H), 8.01 (d,J=8.0Hz,1H), 7.66 (dd,J=8.8,2.2Hz,1H), 7.38 (d,J=8.7Hz,1H), 7.34 (d,J=8.4Hz,1H), 1.44 (s,9H).

[0192] Compound PLC-4.4 [ka]

[0193] Compound PLC-4.4 was synthesized from 9-(tert-butyl)-1H,3H-isochromeno[6,5,4-mna]xanthene-1,3-dione (1.191 mmol, 410 mg) and 2-(4-aminophenyl)acetic acid (2.98 mmol, 450 mg) of compound PLC-4.3 in anhydrous DMF (10 mL). The mixture was heated at 160°C for 2 hours. After work-up and precipitation, 579 mg of the product (quantitative yield) was obtained. MS(APCI):C 30 H 23 Calculated value for NO5 (M+H) = 478; measured value: 478. 1 H NMR(400MHz,DMSO-d6) δ 8.48(d,J=7.9Hz,1H), 8.44(d,J=8.3Hz,1H), 8.38(d,J=8.1Hz,1H), 8.27(d,J=2.4Hz,1H), 7 .69(dd,J=8.8,2.3Hz,1H), 7.45~7.38(m,4H), 7.31~7.27(m,2H), 3.68(s,2H), 1.41(s,9H).

[0194] Compound PLC-4 [ka]

[0195] PLC-4 was synthesized in the same manner as PLC-3 from PLC-1.1 (0.050 mmol, 39.9 mg), PLC-4.4's 2-(4-(tert-butyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)phenyl)acetic acid (0.075 mmol, 35.8 mg), DMAP·pTsOH salt (0.100 mmol, 29.4 mg), and EDC·HCl (0.075 mmol, 14.4 mg). The crude product was purified by conventional methods and triturated with hot MeOH. The product was dried in a vacuum oven at approximately 110°C. 44.1 mg of orange solid (91% yield) was obtained. MS(APCI):C 30 H 23 Calculated value (M-) for NO5: 971; Measured value: 971. 1 1H NMR (400 MHz, methylene chloride-d2) δ 8.66(d,J=7.9Hz,1H), 8.59(d,J=8.3Hz,1H), 8.13(d,J=2.3Hz,1H), 8.06(d,J=8.0Hz,1H), 7.64(dd,J=8.7,2.3Hz,1H), 7.62~7.56(m,2H), 7. 39~7.30(m,4H), 7.05(s,2H), 4.27(q,J=7.1Hz,4H), 4.01(s,2H), 2.80 (s,6H), 2.14(s,6H), 1.73(s,6H), 1.44(s,9H), 1.32(t,J=7.1Hz,6H).

[0196] Synthesis of compound PLC-5 [ka]

[0197] Compound PLC-5.1 [ka]

[0198] Bromine (1.98 g, 12 mmol) was added to a mixture of PLC-1.7 (290 mg, 1.0 mmol) in ortho-dichlorobenzene (30 mL). The mixture was heated at 75°C for 30 hours. After cooling to room temperature, the solid was collected by filtration and dried in air to obtain 290 mg of the desired product, a yellow solid. The filtrate was loaded onto silica gel and purified by flash chromatography using hexane / dichloromethane (50% → 100% dichloromethane) as the eluent. The desired fraction was collected, and the solvent was removed to obtain 110 mg of a yellow solid. A total of 400 mg of product was obtained in 89.7% yield. LCMS(APCI-):C 18 Calculated value (M-) for H6Br2O4: 443.9; Measured value: 444. 1 H NMR(400MHz,d2-TCE) δ 9.40(dd,J=8.5,1.5Hz,1H), 8.71(s,1H), 8.67(s,1H), 7.60(ddd,J=8.4,7.1 ,1.5Hz,1H), 7.48(dd,J=8.3,1.4Hz,1H), 7.38(ddd,J=8.5,7.1,1.4Hz,1H).

[0199] Compound PLC-5.2 [ka]

[0200] A mixture of PLC-5.1 (1576-85) (190 mg, 0.426 mmol), 4-(4-aminophenyl)butanoic acid (180 mg, 0.64 mmol), and 4-(N,N-dimethylamino)-pyridine (4 mg) in anhydrous N,N-dimethylformamide (DMF) (4 mL) was heated at 165°C for 2.5 hours. After cooling to room temperature and standing overnight, the solid was collected by filtration, washed with acetone, and vacuum-dried at 90°C for 1 hour to obtain a yellow solid (220 mg, 84.5% yield). LCMS(APCI-):C 28 H 17 Calculated value (M-) for Br2NO5: 604.95; Measured value: 605. 1H NMR(400MHz,DMSO-d6) δ 9.42(dd,J=8.6,1.5Hz,1H), 8.57(d,J=4.6Hz,2H), 7.83~7.68(m,1H), 7.63~7.44(m,2H), 7.34(d,J= 8.3Hz,2H), 7.31~7.16(m,2H), 2.67(dd,J=4.8,2.8Hz,2H), 2.28(t,J=7.4Hz,2H), 1.95~1.80(m,2H).

[0201] Compound PLC-5.3 [ka]

[0202] A mixture of compound PLC-5.2 (100 mg, 0.165 mmol), (3,5-bis(trifluoromethyl)phenyl)boronic acid (170 mg, 0.66 mmol), Pd(dppf)Cl2 (20 mg, 0.027 mmol), and potassium carbonate (138 mg, 1 mmol) in THF / water (5 mL / 0.5 mL) was degassed and then heated at 80°C for 2 hours. After cooling to room temperature, the precipitate was collected by filtration, washed with acetone, and then dried in a vacuum oven at 90°C for 2 hours. A yellow solid (142 mg, 94% yield) was obtained. LCMS(APCI-):C 44 H 23 F 12 Calculated value (M-) for NO5 = 873.14; measured value: 873. 1 H NMR(400MHz,d2-TCE) δ 8.65(s,1H), 8.40(s,1H), 8.17(s,2H), 7.96(d,J=19.3Hz,4H), 7.38(d,J=8.4Hz,1H), 7.33(d,J=8.0Hz,2H), 7.18(d,J=8.0Hz,3H), 6.90(d,J=6.3Hz,2H), 2.72(t,J=7.6Hz,2H), 2.38(t,J=7.4Hz,2H), 2.03~1.93(m,2H).

[0203] Compound PLC-5 [ka]

[0204] A mixture of PLC-3.6 (1576-30) (30 mg, 0.058 mmol), PLC-5.3 (1576-88) (70 mg, 0.08 mmol), DIC (0.1 mL, 0.63 mmol), and DMAP / p-TsOH (30 mg, 0.1 mmol) in DCM (5 mL) was stirred at room temperature for 40 hours. The resulting mixture was then loaded onto silica gel and purified by flash chromatography using DCM / ethyl acetate (0% → 5% ethyl acetate) as the eluent. The desired main orange fraction was collected. After removing the solvent, the resulting solid was washed with methanol. After filtration, the desired product was obtained as an orange solid (61 mg, 77% yield) and dried in air. LCMS(APCI-):C 71 H 52 BF 14 Calculated value for N3O9: 1367.36; Measured value: 1367. 1 H NMR(400MHz,d2-TCE) δ 8.66(s,1H), 8.41(s,1H), 8.18(s,2H), 7.96(d,J=18.8Hz,4H), 7.38(d,J=8.2Hz,3H), 7.20(dd,J=14.5,8.3Hz,3H), 7.02~6.84(m,4H) , 4.19(q,J=7.2Hz,4H), 2.80(m,2H), 2.75(s,6H), 2.61(t,J=7.3Hz,2H), 2.10(m,2H), 2.06(s,6H), 1.64(s,6H), 1.25(t,J=7.1Hz,6H).

[0205] Synthesis of compound PLC-6 [ka]

[0206] Compound PLC-6.1 [ka]

[0207] A mixture of PLC-3.3 (550 mg, 1.5 mmol), 4-(4-aminophenyl)butanoic acid (537 mg, 3 mmol), and DMAP (12.2 mg, 0.1 mmol) in 10 mL of DMF was heated in a microwave reactor at 165°C for 2.5 hours. The resulting solution was added dropwise to 50 mL of acetone with stirring. A precipitate formed, which was filtered and dried overnight in a vacuum oven at 60°C to obtain the desired product as a yellowish-brown solid (0.49 g, 62% yield). LCMS(APCI-):C 28 H 18 Calculated value for BrNO5 = 527.04; Measured value: 527. 1 H NMR(400MHz,DMSO-d6) δ 8.54(d,J=2.3Hz,1H), 8.41(dd,J=9.9,8.0Hz,2H), 8.33(d,J=7.9Hz,1H), 7.71(dd,J=8.8,2.3Hz,1H), 7.39(dd,J=8. 6,4.2Hz,2H), 7.25(d,J=8.0Hz,2H), 7.17(d,J=7.9Hz,2H), 2.63~2.55(m,2H), 2.27~2.15(m,2H), 1.87~1.73(m,2H).

[0208] Compound PLC-6.2 [ka]

[0209] A mixture of PLC-6.1 (385 mg, 0.729 mmol), 3,5-bis-(trifluoromethyl)phenylboronic acid (374 mg, 1.45 mmol), Pd(dppf)Cl2 (36 mg, 0.05 mmol), and potassium carbonate (276 mg, 2 mmol) in a cosolvent of THF / DMF / water (20 mL / 4 mL / 2 mL) was degassed and then heated overnight at 80°C. The mixture was post-treated with 200 mL of ethyl acetate and 50 mL of 0.6 N hydrochloric acid aqueous solution. The aqueous layer was extracted with ethyl acetate (100 mL x 2). The organic phase was collected, washed with brine (100 mL x 2), dried over sodium sulfate, and then dry-loaded onto silica gel. It was purified by flash chromatography using DCM / EA (0% → 40% EA containing 0.1% TFA) as the eluent. The main desired fraction was collected, and the solvent was removed under reduced pressure to obtain a yellow solid (340 mg, 70.5% yield). LC-MS(APCI-):C 36 H 21 Calculated value for F6NO5 = 661.13; measured value: 661. 1 H NMR(400MHz,d2-TCE) δ 8.57(dd,J=19.2,8.1Hz,2H), 8.18(d,J=2.2Hz,1H), 8.05(d,J=8.0Hz,1H), 8.03~7.98(m,2H), 7.87(s,1H), 7.72(dd,J=8.6,2.2Hz,1 H), 7.48(d,J=8.6Hz,1H), 7.33(d,J=8.3Hz,3H), 7.21~7.12(m,2H), 2.72(t,J=7.6Hz,2H), 2.39(t,J=7.3Hz,2H), 2.04~1.97(m,2H).

[0210] Compound PLC-6 [ka]

[0211] A mixture of PLC-6.2 (49 mg, 0.075 mmol), PLC-3.6 (25.6 mg, 0.05 mmol), DMAP / TsOH salt (20 mg, 0.068 mmol), and DIC (0.1 mL, 0.63 mmol) in 5 mL of DCM was stirred overnight at room temperature. The reaction mixture was placed on silica gel and purified by flash chromatography using DCM / ethyl acetate (0% → 10% ethyl acetate) as the eluent. The desired product peak was collected and concentrated under reduced pressure. The resulting solid was further washed with methanol and dried in air to obtain an orange solid (50 mg, 86%). LCMS(APCI-):C 63 H 50 Calculated value (M-) for BF8N3O9: 1155.35; Measured value: 1155. 1 H NMR(400MHz,d2-TCE) δ 8.60(d,J=7.9Hz,1H), 8.55(d,J=8.4Hz,1H), 8.18(d,J=2.2Hz,1H), 8.05(d,J=8.1Hz,1H), 8.03~7 .99(m,2H), 7.87(s,1H), 7.72(dd,J=8.6,2.2Hz,1H), 7.48(d,J=8.6Hz,1H), 7.36(dd,J=15.9,8.2 Hz,3H), 7.21(d,J=8.2Hz,2H), 6.93(s,2H), 4.19(q,J=7.1Hz,4H), 2.81(t,J=7.5Hz,2H), 2.75(s, 6H), 2.62(t,J=7.4Hz,2H), 2.11(t,J=7.5Hz,2H), 2.06(s,6H), 1.65(s,6H), 1.25(t,J=7.1Hz,6H).

[0212] Synthesis of compound PLC-7 [ka]

[0213] Compound PLC-7.1 [ka]

[0214] A mixture of 1H,3H-thioxantheno[2,1,9-def]isochromen-1,3-dione (458 mg, 1.5 mmol), 4-(4-aminophenyl)butanoic acid (537 mg, 3 mmol), and DMAP (14 mg, 0.11 mmol) in 10 mL of DMF was heated in a microwave reactor at 165°C for 2.5 hours. The resulting solution was added dropwise to 60 mL of acetone with stirring. An orange precipitate was formed, filtered, washed with diethyl ether, and dried in air to obtain an orange solid (546 mg). This was further dried in a vacuum oven at 100°C for 3 hours to obtain the desired product as an orange solid (500 mg, 71.7% yield). Confirmed by LC-MS (APCI-):C 28 H 19 Calculated value (M-) for NO4S: 465.10; Measured value: 465. 1 H NMR(400MHz,DMSO-d6) δ 8.55(d,J=8.4Hz,1H), 8.52~8.46(m,2H), 8.32(d,J=8.0Hz,1H), 7.78(d,J=8.0Hz,1H), 7.65~7.58(m,1H), 7.52(tt,J=7. 2,5.5Hz,2H), 7.37~7.30(m,2H), 7.30~7.23(m,2H), 2.69(t,J=7.4Hz,2H), 2.29(t,J=7.3Hz,2H), 1.88(p,J=7.5Hz,2H).

[0215] Compound PLC-7 [ka]

[0216] A mixture of PLC-3.6 (25.6 mg, 0.05 mmol), PLC-7.1 (35 mg, 0.075 mmol), EDC·HCl (110 mg, 0.57 mmol), and DMAP / p-TsOH (20 mg, 0.068 mmol) in DCM (5 mL) was stirred overnight at room temperature. The resulting mixture was then loaded onto silica gel and purified by flash chromatography using DCM / ethyl acetate (0% → 5% ethyl acetate) as the eluent. The main green fraction was collected, concentrated under reduced pressure, and then triturated with methanol. After filtration, drying in air yielded an orange solid (40 mg, 83% yield). LCMS(APCI-):C 55 H 48 Calculated value (M-) for BF2N3O8S: 959.32; Measured value: 959. 1 1H NMR (400MHz, d2-TCE) δ 8.56(d,J=8.1Hz,1H), 8.35(d,J=8.0Hz,1H), 8.19(dd,J=8.7,4.4Hz,2H), 7 .51(d,J=8.0Hz,1H), 7.45~7.30(m,5H), 7.20(d,J=8.2Hz,2H), 6.93(s,2H), 4.19(q,J=7.1Hz,4H), 2.80(t,J=7.6Hz,2H), 2.75(s,6H), 2.62(t,J=7.5Hz, 2H), 2.11(q,J=7.6Hz,2H), 2.06(s,6H), 1.65(s,6H), 1.25(t,J=7.1Hz,6H).

[0217] Synthesis of compound PLC-8 [ka]

[0218] Compound PLC-8.1 [ka]

[0219] A mixture of compound PLC-6.1 (385 mg, 0.729 mmol), phenylboronic acid (178 mg, 1.45 mmol), Pd(dppf)Cl2 (36 mg, 0.05 mmol), and potassium carbonate (276 mg, 2 mmol) in a cosolvent of THF / DMF / water (20 mL / 4 mL / 2 mL) was degassed and then heated overnight at 80°C. The mixture was post-treated with 200 mL of ethyl acetate and 50 mL of 0.6 N hydrochloric acid aqueous solution. The aqueous phase was extracted with ethyl acetate (100 mL x 2). The organic phase was collected, washed with brine (100 mL x 2), dried over sodium sulfate, and then dry-loaded onto silica gel. It was purified by flash chromatography using DCM / EA (0% → 40% EA containing 0.1% TFA) as the eluent. The main desired fraction was collected, and the solvent was removed under reduced pressure to obtain a yellow solid (250 mg, 65% yield). LCMS(APCI-):C 34 H 23 Calculated value for NO5: 525.16; Measured value: 525. 1 H NMR(400MHz,TCE-d2) δ 8.55(dd,J=19.5,8.1Hz,2H), 8.20(d,J=2.1Hz,1H), 8.01(d,J=8.1Hz,1H), 7.72(dd,J=8.6,2.1Hz,1H), 7.62(d,J=7.3 Hz,2H), 7.51~7.28(m,7H), 7.17(d,J=8.2Hz,2H), 2.72(t,J=7.7Hz,2H), 2.39(t,J=7.3Hz,2H), 1.99(q,J=7.2Hz,2H).

[0220] Compound PLC-8 [ka]

[0221] A mixture of compounds PLC-8.1 (39.4 mg, 0.075 mmol), PLC-3.6 (25.6 mg, 0.05 mmol), DIC (0.1 mL, 0.63 mmol), and DMAP / TsOH (20 mg, 0.068 mmol) in DCM (5 mL) was stirred overnight at room temperature. The resulting mixture was loaded onto silica gel and purified by flash chromatography using DCM / EA (0% → 10% EA) as the eluent. The desired main fraction was collected, concentrated under reduced pressure, and reprecipitation in DCM / methanol to obtain an orange solid (45 mg, 88% yield). LCMA(APCI-):C 61 H 52 Calculated value for BF2N3O9: 1019.38; Measured value: 1019. 1 H NMR(400MHz,d2-TCE) δ 8.56(dd,J=19.5,8.1Hz,2H), 8.20(d,J=2.1Hz,1H), 8.02(d,J=8.1Hz,1H), 7.73(dd,J=8.6,2.1H z,1H), 7.66~7.58(m,2H), 7.45(q,J=8.4,7.9Hz,3H), 7.37(dd,J=7.8,5.7Hz,3H), 7.32(d,J=8.4H z,1H), 7.21(d,J=8.2Hz,2H), 6.93(s,2H), 4.19(q,J=7.1Hz,4H), 2.81(t,J=7.6Hz,2H), 2.75(s,6 H), 2.62(t,J=7.5Hz,2H), 2.11(q,J=7.6Hz,2H), 2.06(s,6H), 1.65(s,6H), 1.25(t,J=7.1Hz,6H).

[0222] Synthesis of compound PLC-9 [ka]

[0223] Compound PLC-9.1 [ka]

[0224] A mixture of 4-bromo-1,8-naphthalic anhydride (2.77 g, 10 mmol) and 4-bromo-2-nitrophenol (3.27 g, 15 mmol) was degassed under vacuum for 30 minutes, then anhydrous NMP (50 mL) was added, followed by sodium hydroxide (0.2 g, 5 mmol) and copper powder (0.318 g, 5 mmol). The mixture was sprayed with argon for 20 minutes, and then heated overnight at 180 °C under an argon atmosphere. After cooling to room temperature, 50 mL of 20% aqueous hydrochloric acid solution was added dropwise to the solution, followed by 50 mL of water. The resulting mixture was left to stand for 3 hours, then filtered to collect the precipitate, which was dried under vacuum to obtain 4.6 g of crude product. The crude product was dispersed in 30 mL of acetone and stirred overnight at room temperature to dissolve impurities. The mixture was filtered and dried under vacuum to obtain the desired product, a yellowish-brown solid (3.3 g, 80% yield). LCMS(APCI+):C 18 Calculated value (M+H) for H9BrNO6: 413.95; Measured value: 414. 1 H NMR(400MHz,TCE-d2) δ 8.70(dd,J=8.4,1.2Hz,1H), 8.63(dd,J=7.3,1.2Hz,1H), 8.41(d,J=8.3Hz,1H), 8.2 4(d,J=2.4Hz,1H), 7.89~7.79(m,2H), 7.20(d,J=8.7Hz,1H), 6.82(d,J=8.3Hz,1H).

[0225] Compound PLC-9.2 [ka]

[0226] A mixture of PLC-9.1 (1.5 g, 3.6 mmol) and iron powder (0.60 g, 10.8 mmol) in acetic acid (50 mL) was heated at 125°C for 30 minutes. After cooling to room temperature, 100 mL of water was added to the mixture while stirring. The resulting mixture was filtered, washed with water, and dried in air and under vacuum to obtain a solid (1.35 g, 82% yield). LCMS(APCI-):C 18 H 10 Calculated value for BrNO4: 382.98; Measured value: 383. 1H NMR (400MHz, DMSO-d6) δ 9.01~8.26 (m, 3H), 7.96 (s, 1H), 6.93 (dd, J=85.2, 36.5Hz, 4H), 5.54 (s, 2H).

[0227] Compound PLC-9.3 [ka]

[0228] PLC-9.2 (2.65 g, 6.9 mmol) was dispersed in acetic acid (50 mL) / water (10 mL) and cooled to 0°C. While stirring, pre-cooled hydrochloric acid (2.8 mL, 34.5 mmol) was added, and then sodium nitrite solution (3.57 g, 52 mmol) in 15 mL of water was added dropwise at 0°C. After stirring the entire mixture at 0°C for 1 hour, it was transferred to an additional funnel and copper sulfate solution (12 g, 47 mmol, 140 mL of water) was added dropwise over 1 hour at 130°C. After cooling to room temperature, the precipitate was collected by filtration, washed with water (100 mL x 3), then stirred in 50 mL of acetone at 40°C for 30 minutes, filtered, dried in air, and then under vacuum to obtain a yellowish-brown solid (1.76 g, 70% yield). LCMS(APCI+):C 18 Calculated value (M+H) for H8BrO4: 366.95; Measured value: 367. 1 H NMR(400MHz,d2-TCE) δ 8.51(dd,J=12.3,8.1Hz,2H), 8.12(d,J=2.3Hz,1H), 7.86(d,J=7.9Hz,1H), 7.60(dd,J=8.8,2.3Hz,1H), 7.28(d,J=8.3Hz,1H), 7.23(d,J=8.8Hz,1H).

[0229] Compound PLC-9.4 [ka]

[0230] A mixture of PLC-9.3 (550 mg, 1.5 mmol), 4-(4-aminophenyl)butanoic acid (537 mg, 3 mmol), and DMAP (12.2 mg, 0.1 mmol) in 10 mL of DMF was heated in a microwave reactor at 165°C for 2.5 hours. The resulting solution was added dropwise to 50 mL of acetone with stirring. A precipitate formed, which was filtered and dried overnight in a vacuum oven at 60°C to obtain the desired product as a yellowish-brown solid (0.49 g, 62% yield). LCMS(APCI-):C 28 H 18 Calculated value for BrNO5 = 527.04; Measured value: 527. 1 H NMR(400MHz,DMSO-d6) δ 8.54(d,J=2.3Hz,1H), 8.41(dd,J=9.9,8.0Hz,2H), 8.33(d,J=7.9Hz,1H), 7.71(dd,J=8.8,2.3Hz,1H), 7.39(dd,J=8. 6,4.2Hz,2H), 7.25(d,J=8.0Hz,2H), 7.17(d,J=7.9Hz,2H), 2.63~2.55(m,2H), 2.27~2.15(m,2H), 1.87~1.73(m,2H).

[0231] Compound PLC-9.4 Compound PLC-9.5 [ka]

[0232] A mixture of PLC-9.4 (385 mg, 0.729 mmol), 3,5-bis-(trifluoromethyl)phenylboronic acid (374 mg, 1.45 mmol), Pd(dppf)Cl2 (36 mg, 0.05 mmol), and potassium carbonate (276 mg, 2 mmol) in a cosolvent of THF / DMF / water (20 mL / 4 mL / 2 mL) was degassed and then heated overnight at 80°C. The mixture was post-treated with 200 mL of ethyl acetate and 50 mL of 0.6 N hydrochloric acid aqueous solution. The aqueous phase was extracted with ethyl acetate (100 mL x 2). The organic phase was collected, washed with brine (100 mL x 2), dried over sodium sulfate, and then dry-loaded onto silica gel. It was purified by flash chromatography using DCM / EA (0% → 40% EA containing 0.1% TFA) as the eluent. The main desired fraction was collected, and the solvent was removed under reduced pressure to obtain a yellow solid (340 mg, 70.5% yield). LC-MS(APCI-):C 36 H 21 Calculated value for F6NO5 = 661.13; measured value: 661. 1 H NMR(400MHz,d2-TCE) δ 8.57(dd,J=19.2,8.1Hz,2H), 8.18(d,J=2.2Hz,1H), 8.05(d,J=8.0Hz,1H), 8.03~7.98(m,2H), 7.87(s,1H), 7.72(dd,J=8.6,2.2Hz,1 H), 7.48(d,J=8.6Hz,1H), 7.33(d,J=8.3Hz,3H), 7.21~7.12(m,2H), 2.72(t,J=7.6Hz,2H), 2.39(t,J=7.3Hz,2H), 2.04~1.97(m,2H).

[0233] Compound PLC-1.1 [ka]

[0234] Step 1: A mixture of ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (1.0 g, 6.0 mmol), 4-hydroxy-2,6-dimethylbenzaldehyde (0.449 g, 3.0 mmol), and tosylic acid (50 mg, 0.29 mmol) in 50 mL of 1,2-dichloroethane was degassed and stirred overnight at room temperature. LCMS analysis was performed, and the results were m / e + It shows one main peak at =467.

[0235] Step 2: Add DDQ (0.817 g, 3.6 mmol) to the obtained solution and stir at room temperature for 30 minutes. LC-MS analysis showed that all starting materials were m / e + =465 indicates that the desired product was converted.

[0236] Step 3: Under ice bath cooling, 1.7 mL of triethylamine and 2.2 mL of BF3-diethyl ether were sequentially added to the mixture from Step 2. The whole was heated at 50°C for 1 hour. LCMS analysis showed approximately 30% conversion. An additional 1 mL of triethylamine and 1 mL of BF3-diethyl ether were added to this mixture, and the whole was heated at 50°C for another 1 hour. LCMS analysis showed that all starting materials were m / e + = 513, m / e - A result of 512 indicates conversion to the desired BODIPY product. The reaction mixture was directly subjected to silica gel and purified by flash chromatography using hexane / ethyl acetate (0% → 30% ethyl acetate) as the eluent. The main desired peak was collected, and the solvent was removed to obtain an orange solid (1.0 g, 65% yield). LCMS(APCI):C 27 H 32 Calculated value (M+H) for BF2N2O5: 513.2; Measured value: 513. 1 ¹H NMR (400MHz, chloroform-d) δ 7.26 (s, 3H), 6.68 (s, 2H), 4.29 (q, J=7.1Hz, 4H), 2.84 (s, 6H), 2.05 (s, 6H), 1.34 (t, J=7.1Hz, 6H).

[0237] Compound PLC-9 [ka]

[0238] A mixture of PLC-9.5 (49 mg, 0.075 mmol), PLC-3.6 (25.6 mg, 0.05 mmol), DMAP / TsOH salt (20 mg, 0.068 mmol), and DIC (0.1 mL, 0.63 mmol) in 5 mL of DCM was stirred overnight at room temperature. The reaction mixture was placed on silica gel and purified by flash chromatography using DCM / ethyl acetate (0% → 10% ethyl acetate) as the eluent. The desired product peak was collected and concentrated under reduced pressure. The resulting solid was further washed with methanol and dried in air to obtain an orange solid (50 mg, 86%). LCMS(APCI-):C 63 H 50 Calculated value (M-) for BF8N3O9: 1155.35; Measured value: 1155. 1 H NMR(400MHz,d2-TCE) δ 8.60(d,J=7.9Hz,1H), 8.55(d,J=8.4Hz,1H), 8.18(d,J=2.2Hz,1H), 8.05(d,J=8.1Hz,1H), 8.03~7 .99(m,2H), 7.87(s,1H), 7.72(dd,J=8.6,2.2Hz,1H), 7.48(d,J=8.6Hz,1H), 7.36(dd,J=15.9,8.2 Hz,3H), 7.21(d,J=8.2Hz,2H), 6.93(s,2H), 4.19(q,J=7.1Hz,4H), 2.81(t,J=7.5Hz,2H), 2.75(s, 6H), 2.62(t,J=7.4Hz,2H), 2.11(t,J=7.5Hz,2H), 2.06(s,6H), 1.65(s,6H), 1.25(t,J=7.1Hz,6H).

[0239] Synthesis of compound PLC-10 [ka]

[0240] Compound PLC-10.1 [ka]

[0241] A 1 L 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. The system was flushed with argon. 6-bromo-1H,3H-benzo[de]isochromen-1,3-dione (40.0 mmol, 11.084 g) and 4-(tert-butyl)-2-nitrophenol (60.0 mmol, 11.712 g) were added to the flask, followed by anhydrous NMP (150 mL). NaOH (20.0 mmol, 800 mg) and copper (powder) (20.0 mmol, 1271 mg) were added to the flask, followed by anhydrous NMP (25 mL). The flask was stirred under an argon atmosphere with the heat block set to 170°C. The reaction mixture was stirred at this temperature overnight. The reaction mixture was cooled to room temperature and treated with water (175 mL) and 1N HCl (44 mL). The reaction mixture was stirred for 30 minutes, then filtered and washed with water. The precipitate was transferred to a flask containing acetone / DCM, evaporated to dryness, and then azeotropically mixed with toluene. The crude product was dissolved in a small amount of DCM and treated with methanol (300 mL). Part of the DCM and methanol were removed by rotary evaporation using a hot water bath (80°C). Once all the DCM had been removed, the mixture was cooled to room temperature and the solid was filtered off. 8.180 g of a dark-colored powder (yield 52%) was obtained. MS(APCI):C 22 H 17 Calculated value for NO6 (M+H) = 392; measured value: 392. 1 ¹H NMR (400MHz, tetrachloroethane-d2) δ 8.82 (dd, J=8.4, 1.2Hz, 1H), 8.71 (dd, J=7.3, 1.2Hz, 1H), 8.49 (d, J=8.3Hz, 1H), 8.16 (d, J=2.4Hz, 1H), 7.91 (dd, J=8.4, 7.3Hz, 1H), 7.80 (dd, J=8.6, 2.4Hz, 1H), 7.34 (d, J=8.6Hz, 1H), 6.91 (d, J=8.3Hz, 1H), 1.43 (s, 9H).

[0242] Compound PLC-10.2 [ka]

[0243] A 250 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. The system was flushed with argon. PLC-10.1 (10.0 mmol, 3.914 g) and 2-MeTHF (70 mL) were added to the flask. While stirring at room temperature, HCl (100 mmol, 4.0 N, 25 mL) and SnCl2·2H2O (40.0 mmol, 9.024 g) were added. Under an argon atmosphere, the reaction mixture was stirred for 30 minutes with the heat block set to 90°C. The reaction mixture was cooled to 0°C and made basic with 2N NaOH aqueous solution to a pH of approximately 8 (pH paper). The solid was filtered off (slow filtration), and the obtained solid was then washed with 2-MeTHF (8 × 100 mL). The filtrate was transferred to a separatory funnel and the layers were separated. The organic layer was dried over MgSO4, filtered, and evaporated to dryness under vacuum. 3.743 g (quantitative yield) was obtained. It was used in the next step without further purification. MS(APCI):C 22 H 19 Calculated value for NO4 (M+H) = 362; measured value: 362. 1 ¹H NMR (400MHz, tetrachloroethane-d2) δ 8.88 (dd, J=8.4, 1.2Hz, 1H), 8.69 (dd, J=7.3, 1.2Hz, 1H), 8.48 (d, J=8.4Hz, 1H), 7.89 (dd, J=8.4, 7.3Hz, 1H), 7.03~6.93 (m, 3H), 6.88 (dd, J=8.4, 2.3Hz, 1H), 1.35 (s, 9H).

[0244] Compound PLC-10.3 [ka]

[0245] A stirring bar, NaNO2 (30.0 mmol, 2.070 g), and water (10 mL) were placed in a 40 mL vial. The vial was stirred in an ice bath at 0°C. A stirring bar and PLC-10.2 (4.00 mmol, 1.446 g) were placed in a 100 mL round-bottom flask. Ice AcOH (30 mL) and concentrated HCl (20.0 mmol, 12.1 N, 1.65 mL) were added to the flask. The mixture was stirred at room temperature for several minutes, then placed in an ice bath and stirred for about 1 minute. The NaNO2 solution was added before the acetic acid began to freeze. The NaNO2 was added over about 10 minutes. The diazo solution was stirred at 0°C for 1 hour. While stirring the diazo solution, a 250 mL 2N round-bottom flask with a large stirring bar was prepared. A finned condenser and dropping funnel were attached to the flask. The flask was clamped at an off-center neck, and the dropping funnel was placed at an off-center neck, so that the solution hit the top of the vortex during stirring. CuSO4·5H2O (27.4 mmol, 6.842 g) and water (80 mL) were added to this flask. About 15 minutes before the diazo solution was obtained, the copper solution was started to heat to 130°C. When the solution reached 130°C, the diazo solution was transferred to the dropping funnel and added dropwise while stirring at high speed for about 30 minutes. After the addition was complete, the solution was heated for a further 1-2 minutes and then cooled in a water bath at room temperature. The precipitate was filtered off and washed with water. The precipitate was dried by suction, and then the crude precipitate was dissolved / suspended in DCM and evaporated to dryness on about 10 g of flash silica gel. Purified by silica gel flash chromatography (220 g, solids, equilibration 50% DCM / hexane, elution 50% DCM / hexane (2 CV) → 100% DCM (20 CV) → isocratic DCM (15 CV) → 0% Â / DCM (0 CV) → 1% Â / DCM (10 CV)). Product tail. The fraction containing the product was evaporated to dryness under vacuum. 528 mg (38% yield) was obtained. MS(APCI):C 22 H 16 Calculated value for O4 (M+H) = 345; measured value: 345. 1¹H NMR (400MHz, tetrachloroethane-d2) δ 8.61 (d,J=7.9Hz,1H), 8.56 (d,J=8.4Hz,1H), 8.05 (d,J=2.2Hz,1H), 8.01 (d,J=8.0Hz,1H), 7.66 (dd,J=8.8,2.2Hz,1H), 7.38 (d,J=8.7Hz,1H), 7.34 (d,J=8.4Hz,1H), 1.44 (s,9H).

[0246] Compound PLC-10.4 [ka]

[0247] PLC-10.4 was synthesized in the same manner as for PLC-1 from PLC-10.3 (1.525 mmol, 525 mg), 4-(4-aminophenyl)butanoic acid (3.05 mmol, 546 mg), and DMAP (0.111 mmol, 14 mg). The crude reaction mixture was diluted with acetone (25 mL) and water (50 mL). The resulting precipitate was filtered and washed with 1:1 acetone:water. The resulting solid was dried in a vacuum oven at approximately 110°C. A yellow solid, 738 mg (96% yield), was obtained. MS(APCI):C 32 H 27 Calculated value for NO5 (M+H) = 506; measured value: 506. 1 H NMR(400MHz,DMSO-d6) δ 12.12(s,1H), 8.48~8.29(m,3H), 8.23(d,J=2.3Hz,1H), 7.68(dd,J=8.8,2.3Hz,1H), 7.43~7.30(m,4H ), 7.25(d,J=7.9Hz,2H), 2.75~2.64(m,2H), 2.30(t,J=7.4Hz,2H), 1.88(p,J=7.5Hz,2H), 1.41(s,9H).

[0248] Compound PLC-10 [ka]

[0249] Compound 10 was synthesized in the same manner as for Compound 2 from PLC-1.1 (0.050 mmol, 25.6 mg), PLC-10.4 (0.075 mmol, 37.9 mg), DMAP·pTsOH salt (0.100 mmol, 29.4 mg), and EDC·HCl (0.075 mmol, 14.4 mg). The crude reaction mixture was diluted with hexane (20 mL) and loaded onto approximately 15 g of flash silica gel in a loader. The mixture was purified by flash chromatography (120 g, solids, equilibration 80% DCM / hexane, elution 80% DCM / hexane (2 CV) → 100% DCM (10 CV) → isocratic DCM (10 CV) → 0% siRNA / DCM (0 CV) → 2% siRNA / DCM (30 CV)). The fraction containing the product was evaporated to dryness. The product was triturated with hot MeOH. The solid was dried in a vacuum oven at approximately 110°C. An orange solid, 46.5 mg (93% yield), was obtained. MS(APCI):C 57 H 52 Calculated value (M-) for BF2N3O9: 999; measured value: 999. 1 ¹H NMR (400MHz, tetrachloroethane-d2) δ 8.66 (d,J=7.9Hz,1H), 8.60 (d,J=8.4Hz,1H), 8.08 (d,J=2.3Hz,1H), 8.05 (d,J=8.1Hz,1H), 7.64 (dd,J=8.8,2.2Hz,1H), 7.49~7.43 (m,2H), 7.41~7.34 (m,2H), 7.32 ~7.27(m,2H), 7.02(s,2H), 4.28(q,J=7.1Hz,4H), 2.89(t,J=7.6Hz,2H), 2.84(s, 6H), 2.71(t,J=7.4Hz,2H), 2.26~2.11(m,8H), 1.45(s,9H), 1.34(t,J=7.1Hz,6H).

[0250] Synthesis of compound PLC-11 [ka]

[0251] Compound PLC-11.1 [ka]

[0252] PLC-6.3 (6.3 g, 17.159 mmol, 1 equivalent) was suspended in 35 mL of anhydrous DMSO, and glycine (2.31 g, 30.77 mmol, 1.8 equivalents) was added to the reaction mixture at room temperature. The resulting mixture was stirred at 130 °C for 1 hour (the mixture did not dissolve), then heated to 160 °C for 1 hour, and LMCMS indicated that the reaction was complete. After cooling to room temperature, the solid product was filtered, washed with water (250 mL), and then dried in a vacuum oven to obtain 6.5 g of a greenish-yellow solid (90% yield). MS(APCI):C 20 H 10 Calculated value (MH) for BrNO5: 423; measured value: 423. 1H NMR (400MHz, DMSO-d6) δ: 8.65 (s, 1H), 8.50 (s, 1H), 8.46 (d, J=8.2Hz, 2H), 8.09 (d, J=8.0Hz, 2H), 7.99 (d, J=8.7Hz, 1H), 7.87 (d, J=8.0Hz, 2H), 7.58 (d, J=8.6Hz, 1H), 7.45 (d, J=8.4Hz, 1H), 4.71 (s, 2H).

[0253] Compound PLC-11.2 [ka]

[0254] PLC-11.1 (7.0 g, 16.50 mmol, 1 equivalent) was suspended in 2-MeTHF (150 ml), and 4-(trifluoromethyl)benzeneboronic acid (5.648 g, 29.7 mmol, 1.8 equivalents), K2CO3 (4.65 g, 33 mmol, 2 equivalents), H2O (15 ml), and Pd(dppf)Cl2·DCM (269.5 mg, 0.33 mmol, 0.02 equivalents) were added. After three Vac-Fill Argon cycles, the resulting mixture was stirred and heated at 95°C under an argon atmosphere for 12 hours. The mixture was then cooled to room temperature, stirred with 1N HCl (20 ml) for 15 minutes, and then held at room temperature for 1 hour. The solid was filtered, stirred with DMF at room temperature for 15 minutes, then filtered again, washed with MeOH, and then dried in a vacuum oven to obtain 6.70 g of greenish-yellow solid, which was used in the next step without further purification (83% yield). MS(APCI):C 27 H 14 Calculated value (M-) for F3NO5: 489; measured value: 489. 1 H NMR(400MHz,DMSO-d6) δ 8.52(s,1H), 8.37(q,J=8.1,7.7Hz,3H), 8.04(d,J=7.9Hz,2H), 7.93(d,J=8.7Hz,1H ), 7.84(d,J=8.0Hz,2H), 7.49(d,J=8.6Hz,1H), 7.34(d,J=8.3Hz,1H), 4.67(s,2H).

[0255] Compound PLC-11 [ka]

[0256] PLC-11.2 (73.4 mg, 0.15 mmol, 1.5 equivalents) was suspended in anhydrous DCM (10.0 ml), and PLC-11.3 (51.2 mg, 0.100 mmol, 1 equivalent), DMAP-pTSA (58.8 mg, 0.2 mmol, 2 equivalents), and EDC·HCl (57.5 mg, 0.3 mmol, 3 equivalents) were added. The mixture was stirred at room temperature under an argon atmosphere for 5 hours. The solution was diluted with DCM (150 ml), filtered, and the solid was washed with 50 ml of DCM. The filtrate was collected and loaded onto an 80 g SiO2 column. Elution was performed with Hex-DCM (1 / 1), DCM alone, and then with 0.5% EA in DCM. After washing with MeOH, 87 mg of yellow solid was obtained (78% yield). MS(APCI):C 54 H 43 Calculated value (M-) for BF5N3O9: 983; measured value: 983. 1 1H NMR (400MHz) δ 8.64(d,J=7.9Hz,1H), 8.59(d,J=8.3Hz,1H), 8.20(d,J=2.1Hz,1H), 8.03(d ,J=8.2Hz,1H), 7.72(dd,J=8.5,2.0Hz,4H), 7.46(d,J=8.6Hz,1H), 7.34(d,J =8.4Hz,1H), 7.01(s,2H), 5.15(s,2H), 4.17(q,J=7.1Hz,4H), 2.74(s,6H), 2.06(s,5H), 1.96(s,1H), 1.61(s,5H), 1.51(s,12H), 1.23(t,J=7.1Hz,5H).

[0257] Synthesis of compound PLC-12 [ka]

[0258] PLC-11.2 (73.4 mg, 0.15 mmol, 3 equivalents) was suspended in anhydrous DCM (10.0 ml), and PLC-12.1 (39.93 mg, 0.05 mmol, 1 equivalent), DMAP-pTSA (58.8 mg, 0.2 mmol, 4 equivalents), and EDC·HCl (47.92 mg, 0.25 mmol, 5 equivalents) were added. The mixture was stirred at room temperature under an argon atmosphere for 5 hours, diluted with DCM (150 ml), filtered, the solid was washed with 50 ml of DCM, the filtrate was collected and loaded onto an 80 g SiO2 column. Elution was performed with Hex-DCM (1 / 1), DCM alone, then with 0.5% EA in DCM, followed by washing with MeOH to obtain 80 mg in 77% yield. MS(APCI):C 64 H 47 Calculated value (M-) for BF5N3O9: 1107; measured value: 1107. 1 H NMR(400MHz,) δ 8.64(d,J=7.9Hz,1H), 8.59(d,J=8.4Hz,1H), 8.20(d,J=2.1Hz,1H), 8.03(d,J=8.1Hz,1H), 7.72(dd,J=8.5,2.1Hz,4H), 7.46(d,J=8 .6Hz,1H), 7.34(d,J=8.3Hz,1H), 7.32~7.18(m,9H), 7.00(s,2H), 5.17(s,4H), 5.14(s,2H), 2.74(s,6H), 2.04(s,6H), 1.61(s,6H).

[0259] Synthesis of compound PLC-13 [ka]

[0260] Compound PLC-13.1 [ka]

[0261] PLC-6.1 (6.3 g, 17.159 mmol, 1 equivalent) was suspended in 35 mL of anhydrous DMSO, and glycine (2.31 g, 30.77 mmol, 1.8 equivalents) was added to the reaction mixture at room temperature. The resulting mixture was stirred at 130 °C for 1 hour (the mixture did not dissolve), then heated to 160 °C for 1 hour, and LMCMS indicated that the reaction was complete. After cooling to room temperature, the solid product was filtered, washed with water (250 mL), and then dried in a vacuum oven to obtain 6.5 g of a greenish-yellow solid (90% yield). MS(APCI):C 20 H 10 Calculated value (MH) for BrNO5: 423; Measured value: 423. 1 H NMR(400MHz,DMSO-d6) δ 8.65(s,1H), 8.50(s,1H), 8.46(d,J=8.2Hz,2H), 8.09(d,J=8.0Hz,2H), 7.99(d,J=8.7H) z,1H), 7.87(d,J=8.0Hz,2H), 7.58(d,J=8.6Hz,1H), 7.45(d,J=8.4Hz,1H), 4.71(s,2H).

[0262] Compound PLC-13.2 [ka]

[0263] PLC-13.1 (4.24 g, 10.0 mmol, 1 equivalent) was suspended in 2-MeTHF (150 ml) and H2O (5.0 ml), and 4-(tert-butyl)benzeneboronic acid (3.56 g, 20 mmol, 2 equivalents), K2CO3 (2.76 g, 20 mmol, 2 equivalents), and Pd(dppf)Cl2·DCM (163.3 mg, 0.2 mmol, 0.02 equivalents) were added. The reaction mixture was degassed three times using a Vac-Fill argon cycle and heated and stirred at 95°C for 12 hours under an argon atmosphere. After cooling to room temperature, ethyl acetate (150 ml) acidified to pH 4-5 with 1N HCl was added. The organic layer was washed with water, separated, and concentrated. The residue was stirred in DMF (15 ml), filtered to obtain a solid, washed with MeOH (50 mL), and then dried in a vacuum oven to obtain 4.1 g of a greenish-yellow solid product (85% yield). MS(APCI):C 30 H 23 Calculated value (M-) for NO5: 477; Measured value: 477. 1 H NMR(400MHz,DMSO-d6) δ 8.33(d,J=6.1Hz,3H), 8.24(d,J=7.9Hz,1H), 7.95(s,1H), 7.78(d,J=8.3Hz,1H), 7.70(d,J=7.9Hz,2H), 7.50(d,J=7.9Hz,2 H), 7.39(d,J=8.3Hz,1H), 7.29(d,J=8.2Hz,1H), 4.52(s,2H), 2.89(s,3H), 2.73(s,3H), 2.54~2.47(m,21H), 1.34(s,10H).

[0264] Compound PLC-13 [ka]

[0265] PLC-13.2 (71.62 mg, 0.15 mmol, 1.5 equivalents) was suspended in anhydrous DCM (10.0 ml), PLC-13.3 (58.5 mg, 0.1 mmol, 1 equivalent), DMAP-pTSA (58.8 mg, 0.2 mmol, 2 equivalents), and EDC·HCl (57.5 mg, 0.3 mmol, 3 equivalents) were added, and the mixture was stirred at room temperature under an argon atmosphere for 5 hours. The mixture was diluted with DCM (150 ml), filtered, and the solid was washed with 50 ml of DCM. The filtrate was collected and loaded onto an 80 g SiO2 column, and eluted with Hex-DCM (1 / 1), DCM alone, and then with 0.5% EA in DCM. The crude substance was loaded onto an 80 g SiO2 column and eluted with Hex-DCM (1 / 1), DCM alone, then with 0.5% EA in DCM, followed by washing with MeOH to obtain 80 mg in yield of 84.3%. MS(APCI):C 57 H 52 Calculated value (M-) for BF2N3O9: 971; measured value: 971. 1 H NMR(400MHz,) δ 8.64(d,J=7.9Hz,1H), 8.59(d,J=8.4Hz,1H), 8.20(d,J=2.1Hz,1H), 8.03(d,J=8.1Hz,1H), 7.72(dd,J=8.5,2.1Hz,4H), 7.46(d,J=8 .6Hz,1H), 7.34(d,J=8.3Hz,1H), 7.32~7.18(m,9H), 7.00(s,2H), 5.17(s,4H), 5.14(s,2H), 2.74(s,6H), 2.04(s,6H), 1.61(s,6H).

[0266] Synthesis of compound PLC-14 [ka]

[0267] PLC-13.2 (71.62 mg, 0.15 mmol, 1.5 equivalents) was suspended in anhydrous DCM (10.0 ml), and PLC-12.1 (63.65 mg, 0.100 mmol, 1 equivalent), DMAP-pTSA (58.8 mg, 0.2 mmol, 2 equivalents), and EDC·HCl (57.5 mg, 0.3 mmol, 3 equivalents) were added. The mixture was stirred at room temperature under an argon atmosphere for 5 hours, diluted with DCM (150 ml), filtered, and the solid was washed with 50 ml of DCM. The filtrate was collected and loaded onto an 80 g SiO2 column. Elution was performed with Hex-DCM (1 / 1), DCM alone, and then with 0.5% EA in DCM. The good fraction was concentrated and then washed with MeOH to obtain a yield of 85 mg, 77%. MS(APCI):C 67 H 56 Calculated value (M-) for BF2N3O9: 1095; measured value: 1095. 1 H NMR(400MHz) δ 8.63(d,J=7.9Hz1H), 8.58(d,J=8.4Hz,1H), 8.21(d,J=2.1Hz,1H), 8.02(d,J=8. 1Hz,1H), 7.73(dd,J=8.6,2.1Hz,1H), 7.56(d,J=8.3Hz,2H), 7.46(d,J=8.4Hz,2 H), 7.42(d,J=8.6Hz,1H), 7.32(d,J=8.4Hz,1H), 7.30~7.17(m,10H), 7.00(s,2H) ), 5.17(s,5H), 5.14(s,2H), 2.74(s,6H), 2.04(s,6H), 1.61(s,6H), 1.31(s,9H).

[0268] Synthesis of compound PLC-15 [ka]

[0269] Compound PLC-3.4 [ka]

[0270] A mixture of PLC-3.3 (400.0 mg, 1.1 mmol), 4-aminophenylacetic acid (329.4 mg, 2.2 mmol), and DMAP (9.3 mg, 0.080 mmol) in DMF (8 mL) was degassed at room temperature. The mixture was then heated to 165°C and held at this temperature for 3 hours. TLC and LC-MS showed approximately 95% conversion without observable side reactions. The mixture was cooled to 50°C. It was then poured into an acetone solution (40 mL) and pre-cooled in an ice bath. The mixture was held at 0°C for 2 hours and then stirred overnight at room temperature. The solid was collected by vacuum filtration and washed with acetone (4 mL). It was then dried in a vacuum oven at 100°C for 3 hours to obtain pure compound PLC-3.4 as a yellowish-brown solid (395.0 mg, 73% yield). MS(APCI):C 26 H 14 Calculated values ​​for BrNO5 ([M+H] + )=500; Measured value: 500. 1 H NMR(400MHz,CDCl2CDCl2) δ 8.65(d,J=8.0Hz,1H), 8.62(d,J=8.0Hz,1H), 8.21(dd,J=6.4Hz,2.4Hz,1H), 7.99(bs,1H), 7.95(t,J=7.6Hz ,1H), 7.67(dd,J=8.4Hz,2.4Hz,1H), 7.53(d,J=8.0Hz,2H), 7.37(d,J=8.4Hz,1H), 7.32(m,3H), 2.94(s,2H).

[0271] Compound PLC-15.1 [ka]

[0272] A mixture of PLC-3.4 (175.0 mg, 0.35 mmol), 4-tert-butylphenylboronic acid (124.6 mg, 0.70 mmol), Pd(dppf)Cl2 (18.0 mg, 0.025 mmol), and K2CO3 (130.4 mg, 0.95 mmol) in THF-DMF-H2O (10 mL / 2 mL / 1 mL) was degassed at room temperature. The mixture was then heated to 80°C and held at this temperature overnight. TLC and LC-MS indicated completion of the reaction. The mixture was cooled to room temperature. Then, 0.1 HCl (75 mL) and  (75 mL) were added. After separation using a separatory funnel, the aqueous solution was saturated with NaCl and then further extracted with THF (75 mL × 3). The combined organic phase was dried over anhydrous Na2SO4, then filtered, concentrated under a rotary evaporator, and purified by silica gel flash chromatography using 0%→40% toluene in DCM containing 0.1% TFA as an eluent, yielding PLC-15.1 (76.0 mg, 39% yield) as a yellow solid. MS(APCI):C 36 H 27 Calculated value for NO5 ([MH]) - )=553; Measured value: 553. 1 H NMR(400MHz,CDCl2CDCl2) δ 8.69(d,J=8.0Hz,1H), 8.64(d,J=8.4Hz,1H), 8.24(d,J=8.4Hz,1H), 8.03(d,J=8.0Hz,1 H), 7.76(dd,J=8.4Hz,2.0Hz,1H), 7.53(m,7H), 7.33(m,4H), 3.77(s,2H), 1.40(s,9H).

[0273] Compound PLC-15 [ka]

[0274] PLC-1.1 (30.0 mg, 0.059 mmol), PLC-15.1 (64.8 mg, 0.12 mmol), EDC·HCl (56.6 mg, 0.30 mmol), and DMAP·TsOH (35.4 mg, 0.12 mmol) were added to a vial, followed by the addition of anhydrous DCM (3 ml). The reaction mixture was kept at room temperature overnight. After the reaction was complete, the mixture was loaded onto silica gel and purified by flash chromatography using DCM in  (0% → 4%) as the eluent to obtain pure RL-naphthalimide-BODIPY PLC-15 as an orange-yellow solid. The solid was further triturated with  (0.5 mL) and MeOH (15 ml) to obtain RL-naphthalimide-BODIPY PLC-15 (48.0 mg, 78% yield). MS(APCI):C 63 H 56 Calculated values ​​for BF2N3O9 ([MH] - )=1047; Measured value: 1047. 1 1H NMR (400MHz, CDCl2CDCl2) 8.68(d,J=8.0Hz,1H), 8.63(d,J=8.0Hz,1H), 8.30(d,J=2.0Hz,1H), 8.10(d,J=8.0Hz,1H), 7.82(dd,J=8.0Hz,2.0Hz,1H), 7.65(m,4H), 7.53(m ,3H), 7.39(m,3H), 7.05(s,2H), 4.28(q,J=7.2Hz,4H), 4.01(s,2H), 2.8 4(s,6H), 2.16(s,6H), 1.74(s,6H), 1.40(s,9H), 1.34(t,J=7.2Hz,6H).

[0275] Synthesis of compound PLC-16 [ka]

[0276] Compound PLC-16.1 [ka]

[0277] A stirring bar was attached to a 100 mL vial. PLC-3.4 (400.0 mg, 0.80 mmol), 3,5-bis(trifluoromethyl)phenylboronic acid (262.2 mg, 1.6 mmol), Pd(dppf)Cl2 (41.0 mg, 0.056 mmol), and K2CO3 (412.6 mg, 2.2 mmol) were degassed at room temperature from THF / DMF / H2O (22 ml / 4.4 ml / 2.2 ml) in the vial. The reaction mixture was heated to 80 °C and the reaction product was held at this temperature overnight. The reaction was monitored using TLC. After completion, the reaction product was work-treated by adding 0.1 N HCl (150 ml) and siRNA (150 ml). The aqueous phase was further extracted with THF (150 ml x 3). The combined organic phases were dried over anhydrous Na2SO4, concentrated under a rotary evaporator, and purified by flash chromatography using DCM in toluene (0% → 40%, containing 0.1% TFA) as an eluent to obtain pure RL-naphthalimide derivative PLC-16.1 as a yellow / yellowish-brown solid (311.0 mg, 61% yield). MS(APCI):C 34 H 17 Calculated values ​​for F6NO5 ([M+H]) + )=634; Measured value: 634. 1 H NMR(400MHz,DMSO-d6) 8.73(m,1H), 8.46(m,5H), 8.10(m,2H), 7.57(m,1H), 7.42(d,J=8.0Hz,2H), 7.40(m,1H), 7.30(d,J=8.0Hz,2H), 3.72(s,2H).

[0278] Compound PLC-16 [ka]

[0279] A stirring bar was attached to a 25 mL vial. PLC-1.1 (40.0 mg, 0.078 mmol), PLC-16.1 (98.9 mg, 0.16 mmol), EDC·HCl (74.8 mg, 0.39 mmol), and DMAP·TsOH (46.8 mg, 0.16 mmol) were added to the vial, followed by the addition of anhydrous DCM (4 ml). The reaction mixture was kept at room temperature overnight. After the reaction was complete, the mixture was loaded onto silica gel and purified by flash chromatography using DCM in  (0% → 4%) as the eluent to obtain pure RL-naphthalimide-BODIPY PLC-16 as an orange-yellow solid. The solid was further triturated with  (0.5 mL) and MeOH (15 ml) to obtain RL-naphthalimide-BODIPY PLC-16 (58.0 mg, 66% yield). MS(APCI):C 61 H 46 Calculated values ​​for BF8N3O9 ([MH] - )=1127; Measured value: 1127. 1 1H NMR (400MHz, CDCl2CDCl2) 8.70(d,J=8.0Hz,1H), 8.65(d,J=8.0Hz,1H), 8.28(d,J=2.4Hz,1H), 8.15(d,J=8.0Hz,1H), 8.11(m,2H), 7.96(bs,1H), 7.81(dd,J=8.0Hz,2.4Hz ,1H), 7.61(m,3H), 7.41(m,3H), 7.05(s,2H), 4.28(q,J=7.2Hz,4H), 4.0 1(s,2H), 2.84(s,6H), 2.16(s,6H), 1.73(s,6H), 1.34(t,J=7.2Hz,6H).

[0280] Synthesis of compound PLC-17 [ka]

[0281] Compound PLC-17.1 [ka]

[0282] A 250 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter and a flow control valve were attached to the flask. The system was flushed with argon. 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (11.0 mmol, 2.421 g), 1-bromo-2-(2-(2-methoxyethoxy)ethoxy)ethane (10.0 mmol, 2.48 mL), anhydrous DMF (25 mL), and K2CO3 (11.0 mmol, 1.520 g) were added to the flask. The reaction mixture was stirred at room temperature under an argon atmosphere for 5 minutes, then the heat block was set to 50°C and the reaction mixture was stirred at 50°C for 6 hours, then stirred at room temperature over the weekend. The reaction mixture was diluted with water (approximately 200 mL) and then extracted with ethyl ether (3 × 100 mL). The combined ether layers were washed with saturated NaHCO3 aqueous solution (50 mL) and brine (50 mL), dried over MgSO4, filtered, and evaporated to dryness under vacuum. A pale yellow oily substance (4.166 g, 114% yield) was obtained. NMR showed that it was a mixture of the desired product and the starting bromoglycol (estimated to be approximately 57% product). This was used in the next step without further purification. MS(APCI):C 19 H 31 Calculated value (M+H) for BO6: 367; Measured value: 367. 1 H NMR (400MHz, methanol-d4) δ 7.69~7.63(m,2H), 6.95~6.90(m,2H), 4.18~4.11(m,2H), 3.86~3.82(m,2 H), 3.72~3.67(m,2H), 3.66~3.60(m,2H), 3.54~3.48(m,4H), 3.34(s,3H).

[0283] Compound PLC-17.2 [ka]

[0284] A 500 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. The system was flushed with argon. 6-bromo-1H,3H-benzo[de]isochromen-1,3-dione (60.0 mmol, 16.626 g) and 4-bromo-2-nitrophenol (120.0 mmol, 26.160 g) were added to the flask, followed by anhydrous NMP (250 mL). NaOH (30.0 mmol, 1200 mg) and copper (powder) (30.0 mmol, 1907 mg) were added to the flask, followed by anhydrous NMP (250 mL). The flask was stirred under an argon atmosphere, the heat block was set to 170°C, and the reaction mixture was stirred at this temperature for 6 hours, then stirred overnight at room temperature. The reaction mixture at room temperature was quenched with an aqueous solution of 1N HCl (60 mL). The reaction mixture was transferred to a 2 L Erlenmeyer flask and diluted with water to approximately 1100 mL while stirring vigorously. The slurry was stirred at room temperature for 1 hour, then the precipitate was filtered off and washed with water. The crude product was dried by suction for approximately 10 minutes, then suspended in methanol (approximately 350 mL) and stirred at room temperature for 45 minutes. The precipitate was filtered off and dried by suction for approximately 10 minutes, then suspended in acetone (120 mL) and stirred at room temperature for 45 minutes. The precipitate was filtered off and washed with a small amount of acetone. The precipitate was dried by suction for approximately 30 minutes, then dried overnight in a vacuum oven at approximately 110°C. 16.54 g of a light brown powder (67% yield) was obtained. MS(APCI):C 18 Calculated value for H8BrNO6: (M+H) = 414; Measured value: 414. 1 H NMR(400MHz,DMSO-d6) δ 8.75(dd,J=8.4,1.1Hz,1H), 8.63(dd,J=7.3,1.1Hz,1H), 8.50(d,J=2.4Hz,1H), 8.44(d,J=8.2Hz,1H), 8.12(dd,J=8.8,2.5Hz,1H), 7.99(dd,J=8.5,7.3Hz,1H), 7.61(d,J=8.8Hz,1H), 7.18(d,J=8.3Hz,1H).

[0285] Compound PLC-17.3 [ka]

[0286] A 1 L 3N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. The system was flushed with argon. PLC-17.2 (26.37 mmol, 10.923 g), SnCl2·2H2O (105.5 mmol, 23.799 g), and HCl (4.0 N, 263.7 mmol, 65.9 mL), followed by 2 MeTHF (185 mL), were added to the flask. The reaction mixture was stirred under argon, and the heat block was set to 90°C. The reaction mixture was stirred at 90°C for 30 minutes and then cooled to room temperature. The mixture was stirred and titrated to approximately pH 8 with aqueous 2N NaOH. The tin salt was removed by filtration, and the filter cake was washed with 2 MeTHF (6 × 50 mL). The aqueous layer was treated with NaCl until saturated, and then the layers were separated. The aqueous layer was extracted with 2 MeTHF (2 × 50 mL), and the combined 2 MeTHF layer was then dried with MgSO4, filtered, evaporated to dryness under vacuum, and the solid was subsequently dried overnight in a vacuum oven at approximately 110°C. 9.444 g (93% yield) was obtained. MS(APCI):C 18 H 10 Calculated value (M+H) for BrNO4: 384; Measured value: 384. 1 ¹H NMR (400MHz, tetrachloroethane-d2) δ 8.86 (dd, J=8.4, 1.2Hz, 1H), 8.68 (dd, J=7.3, 1.2Hz, 1H), 8.48 (d, J=8.3Hz, 1H), 7.89 (dd, J=8.4, 7.3Hz, 1H), 7.11 (d, J=2.1Hz, 1H), 7.03~6.91 (m, 3H).

[0287] Compound PLC-17.4 [ka]

[0288] A stirring bar was placed in a 100 mL recovery flask. NaNO2 (154.9 mmol, 10.688 g) and water (45 mL) were added to the flask. This flask was stirred in an ice bath at 0°C. A stirring bar was placed in another 500 mL recovery flask. PLC-17.3 (20.65 mmol, 7.933 g), acetic acid (150 mL), and concentrated HCl (12.1 N, 103.2 mmol, 8.6 mL) were added to the flask. The mixture was stirred at room temperature for 5 minutes, then cooled in an ice bath at 0°C for about 1 minute. Immediately, the addition of the NaNO2 solution was started. The addition was carried out over about 15 minutes. The crude diazo solution was stirred at 0°C for 1 hour. While stirring the diazo solution, a 1 L 3N round-bottom flask was placed in an aluminum heat block equipped with a large stirring bar and a finned condenser. CuSO4·5H2O (140.4 mmol, 35.059 g) and water (420 mL) were added to a flask. The mixture was stirred at room temperature. About 15 minutes before the diazo solution was finished, the CuSO4 solution was heated to 130°C. The diazo solution was added to the CuSO4 solution over 45 minutes using a peristaltic pump and chemical-resistant tubing while stirring at high speed. After the addition was complete, the mixture was heated at 130°C for about 1 minute, and then rapidly cooled in a water bath at room temperature. The crude product was filtered and washed with water. The crude precipitate was boiled in methanol (about 100 mL), then cooled to 0°C (ice bath), filtered, and washed with methanol. The crude product was then heated in toluene (about 75 mL) to about 95°C, then cooled to 0°C (ice bath), and then left overnight to reach room temperature. The precipitate was filtered and washed with a small amount of toluene. The crude product was dried by vacuum and then dried in a vacuum oven at approximately 110°C. 5.538 g of a yellowish solid (73% yield) was obtained. MS(APCI):C 18 Calculated value for H7BrO4: (M+H) = 367; Measured value: 367. 1 ¹H NMR (400MHz, tetrachloroethane-d2) δ 8.61 (d,J=7.9Hz,1H), 8.58 (d,J=8.4Hz,1H), 8.19 (d,J=2.2Hz,1H), 7.94 (d,J=8.0Hz,1H), 7.69 (dd,J=8.8,2.3Hz,1H), 7.35 (s,0H), 7.31 (d,J=8.8Hz,1H).

[0289] Compound PLC-17.5 [ka]

[0290] A 100 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter and a flow control valve were attached to the flask. The system was flushed with argon. PLC-17.4 (0.702 mmol, 250 mg), 2-(4-aminophenyl)acetic acid (1.754 mmol, 265 mg), and DMAP (0.0512 mmol, 6.3 mg), followed by anhydrous DMF (10 mL), were added to the flask. The reaction mixture was stirred under argon, and the heat block was set to 170°C. The reaction mixture was stirred at 170°C for 9 hours, then stirred at room temperature. The crude reaction mixture was diluted with 75 mL of water. This mixture was stirred for 5 minutes, then the crude product was filtered off and dried by suction for 5 minutes. The wet precipitate was dried overnight in a vacuum oven at approximately 110°C. A yellowish powder, 366 mg (107% yield) was obtained. NMR shows approximately 10% to 15% dimethylamide byproducts. MS(APCI):C 26 H 14 Calculated value (M+H) for BrNO5: 500; Measured value: 500. 1 H NMR(400MHz,DMSO-d6) δ 8.60(d,J=2.3Hz,1H), 8.49~8.45(m,2H), 8.39(d,J=8.1Hz,1H), 7.80~7.75( m,1H), 7.48~7.43(m,2H), 7.43~7.38(m,2H), 7.31~7.27(m,2H), 3.67(s,2H).

[0291] Compound PLC-17.6 [ka]

[0292] A 250 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter and a flow control valve were attached to the flask. The system was flushed with argon. Compound PLC-17.5 (2.00 mmol, 1001 mg), compound 17.1 (4.00 mmol, 1465 mg), K2CO3 (5.50 mmol, 760 mg), and Pd(dppf)Cl2 (0.140 mmol, 102 mg) were added to the flask, followed by THF (60 mL), DMF (12 mL), and water (6 mL). The reaction mixture was stirred under argon and nitrogen was sprayed for 10 minutes. The nitrogen spraying was stopped and stirring under argon was continued. The heat block was set to 80°C for 2 hours. The reaction mixture was quenched with 6N HCl (5 mL) and diluted with water (50 mL) and THF (50 mL). Sodium chloride was added until the aqueous layer was saturated, then the layers were separated and extracted with THF (3 × 50 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered, and evaporated to dryness under vacuum (including DMF). The crude product was evaporated onto approximately 50 g of flash silica gel and placed in a loader. Purification was performed by silica gel flash chromatography (220 g, solids content, equilibrated 100% DCM, elution 100% DCM (2 CV) → 40% (Â / 0.1% TFA) / DCM (20 CV) → 70% (Â / 0.1% TFA) / DCM (20 CV)). The fraction containing the product was evaporated to dryness under vacuum. A yellow solid, 722 mg (55% yield) was obtained. MS(APCI):C 39 H 33 Calculated value for NO9 (M+H) = 660; measured value: 660. 1H NMR(400MHz,DMSO-d6) δ 8.57(d,J=2.2Hz,1H), 8.52(s,2H), 8.48(d,J=8.3Hz,1H), 7.90(dd,J=8.7,2.2Hz,1 H), 7.84~7.78(m,2H), 7.55(d,J=8.7Hz,1H), 7.48(d,J=8.3Hz,1H), 7.41(d,J=8.1H) z,2H), 7.33~7.26(m,2H), 7.12~7.07(m,2H), 4.22~4.14(m,2H), 3.82~3.76(m,2H), 3.68(s,2H), 3.65~3.59(m,2H), 3.58~3.51(m,4H), 3.48~3.41(m,2H), 3.25(s,3H).

[0293] Compound PLC-17 [ka]

[0294] A stirring bar was placed in a 40 mL vial, followed by PLC-17.6 (0.075 mmol, 49.5 mg), PLC-1.1-diethyl 5,5-difluoro-10-(4-hydroxy-2,6-dimethylphenyl)-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate (0.050 mmol, 25.6 mg), DMAP·pTsOH salt (0.100 mmol, 29.4 mg), and EDC·HCl (0.200 mmol, 38.3 mg), followed by anhydrous DCM. The vial was capped, and the reaction mixture was stirred at room temperature overnight. The crude reaction mixture was quenched with a few drops of TFA and loaded onto approximately 65 g of flash silica gel in a loader. The product was purified by silica gel flash chromatography (120 g, solids content, equilibrated 100% DCM, eluted 100% DCM (3 CV) → 10% siRNA / DCM (10 CV) → 40% siRNA / DCM (10 CV)). The fraction containing the product was evaporated to dryness under vacuum. The crude product was dried in a vacuum oven at approximately 110°C. An orange solid, 52 mg (90% yield) was obtained. MS(APCI):C 66 H 62 BF2N3O13 についてのcalculated value (M-)=1153; measured value: 1153. 1 H NMR (400MHz, Tactron-d2) δ 8.68(d,J=7.9Hz,1H), 8.63(d,J=8.4Hz,1H), 8.25(d,J=2.1Hz,1H), 8.11(d,J=8.2Hz,1H), 7.78(dd,J=8.6 ,2.1Hz,1H), 7.68~7.61(m,4H), 7.50(d,J=8.6Hz,1H), 7.43~7.35(m,3H), 7.12~7.07(m,2H), 7.05(s,2H), 4.28(q,J=7.1Hz,4H), 4.22(t,J=4.8Hz,2H), 4.01(s,2H), 3.90(t,J=4.8Hz,2H), 3.78~3.73(m,2H), 3.72~ 3.62(m,4H), 3.59~3.54(m,2H), 3.38(s,3H), 2.84(s,6H), 2.16(s,6H), 1.74(s,6H), 1.34(t,J=7.1Hz,6H).

[0295] Synthesis of compound PLC-18

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[0296] Compound PLC-18.1

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[0297] A 50 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. The system was flushed with argon. PLC-6.3 (3.00 mmol, 1101 mg), ethanolamine (12.0 mmol, 0.725 mL), and DMAP (0.900 mmol, 110 mg) were added to the flask, followed by anhydrous DMF (8 mL). The reaction mixture was stirred under argon, and the heat block was set to 165°C. The reaction mixture was stirred at this temperature for 3 hours, and then cooled to room temperature. The solvent was evaporated to dryness under vacuum. The residue was triturated with water (50 mL) and 6N aqueous HCl (10 mL). The mixture was sonicated for several minutes, then stirred at room temperature for 30 minutes, and the solid product was filtered off and washed with water. The crude filtration cake was dried overnight in a vacuum oven at approximately 110°C. A dark brown solid, 1.038 g (84% yield), was obtained. MS(APCI):C 20 H 12 Calculated value (M+H) for BrNO4: 410; Measured value: 410.

[0298] Compound PLC-18.2 [ka]

[0299] PLC-18.2 was synthesized in the same manner as for PLC-17.6 from PLC-18.1 (2.531 mmol, 1.038 g), (4-(trifluoromethyl)phenyl)boronic acid (5.062 mmol, 961 mg), K2CO3 (6.960 mmol, 962 mg), and Pd(dppf)Cl2 (0.177 mmol, 130 mg) in THF / DMF / H2O (60 mL / 12 mL / 6 mL) over 30 minutes at 80°C. The crude product was precipitated by adding water (100 mL), and the resulting solid was filtered and washed with water. The crude product was triturated with methanol and then dried overnight in a vacuum oven at approximately 110°C. 1.017 g (84% yield) was obtained. MS(APCI):C 27 H 16Calculated value for F3NO4 (M+H) = 476; measured value: 476. 1 H NMR(400MHz,TCE) δ 8.66(d,J=7.8Hz,1H), 8.61(d,J=8.3Hz,1H), 8.25(d,J=2.2Hz,1H), 8.06(d,J=8.0Hz,1H), 7.83~7.75(m,5H), 7 .52(d,J=8.6Hz,1H), 7.37(d,J=8.4Hz,1H), 4.45(t,J=5.2Hz,2H), 3.98(q,J=5.3Hz,2H), 2.49(t,J=5.5Hz,1H).

[0300] Compound PLC-18.3 [ka]

[0301] A 250 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. The system was flushed with argon. PLC-18.2 (2.124 mmol, 1.01 g), pTsCl (6.372 mmol, 1.215 g), anhydrous DMF (20 mL), and Et3N (6.372 mmol, 0.888 mL) were added to the flask. The reaction mixture was stirred under argon and heated at 80°C for 2 hours. An unexpected reaction occurred when the tosylate was replaced in situ by chloride ions. The reaction mixture was cooled to room temperature and diluted with water (100 mL). The crude product was filtered and washed with water. The crude product was tritulated with MeOH. The product was dried overnight in a vacuum oven at approximately 110°C. 974 mg of orange solid (93% yield) was obtained. MS(APCI):C 27 H 15 Calculated value for ClF3NO3 (M+H) = 494; measured value: 494. 1H NMR(400MHz,TCE) δ 8.67(d,J=7.9Hz,1H), 8.62(d,J=8.3Hz,1H), 8.27(d,J=2.2Hz,1H), 8.08(d,J=7.9Hz,1H), 7.86~7.7 3(m,5H), 7.53(d,J=8.6Hz,1H), 7.39(d,J=8.4Hz,1H), 4.56(t,J=6.9Hz,2H), 3.87(t,J=6.8Hz,2H).

[0302] Compound PLC-18.4 [ka]

[0303] A 100 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. PLC-18.3 (0.607 mmol, 300 mg), 4-hydroxy-2,6-dimethylbenzaldehyde (1.336 mmol, 201 mg), and K2CO3 (1.215 mmol, 168 mg) were added to the flask, followed by anhydrous DMF (20 mL). The reaction mixture was stirred under argon, and the heat block was set to 100°C. The reaction mixture was stirred under an argon atmosphere for 8 hours, then stirred overnight at room temperature. The crude reaction mixture was diluted with water (approximately 100 mL), the precipitate was filtered off, and washed with water. The crude product was dissolved in DCM and evaporated to dryness. The crude product was redissolved in DCM and evaporated onto flash silica gel (approximately 20 g). The product was purified by silica gel flash chromatography (120 g, solids content, equilibration 70% hexane / DCM, elution 70% hexane / DCM (2 CV) → 100% DCM / hexane (10 CV) → isocratic 100% DCM / hexane (5 CV) → 0% siRNA / DCM (0 CV) → isocratic 0% siRNA / DCM (10 CV) → 40% siRNA / DCM (40 CV)). The fraction containing the product was evaporated to dryness under vacuum. 48 mg (13% yield) of yellow solid was obtained. MS(APCI):C 36 H 24F3NO0についての calculated value (M-)=607; measured value: 607. 1 H NMR(400MHz,TCE) δ 10.41(s,1H), 8.69(d,J=7.8Hz,1H), 8.64(d,J=8.3Hz,1H), 8.27(d,J=2.1Hz,1H), 8.09(d,J=8.1Hz,1H), 7.85~7.75(m,5 H), 7.53(d,J=8.6Hz,1H), 7.39(d,J=8.3Hz,1H), 6.66(s,2H), 4.65(t,J=6.2Hz,2H), 4.38(t,J=6.2Hz,2H), 2.57(s,6H).

[0304] Compound PLC-18

change

[0305] A 100 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. The system was flushed with argon. PLC-18.4 (0.0741 mmol, 45 mg) and ethyl 2,4-dimethyl-1H-pyrrole-3-carbone carboxylate (0.1556 mmol, 26 mg) were added to the flask, followed by anhydrous DCE (15 mL). Under an argon atmosphere, nitrogen was sprinkled over the reaction mixture for 10 minutes. A few small granular pTsOH·H2O particles were collected at the end of a spatula and immersed in the reaction mixture. Stirring and nitrogen sprinkling were continued for a further 5 minutes. Nitrogen sprinkling was stopped, and the reaction mixture was stirred under an argon atmosphere. The heat block was set to 85°C, and the reaction mixture was stirred at this temperature overnight. TLC showed complete conversion to the desired dipyrrolomethane. The reaction mixture was cooled to room temperature in a water bath. DDQ (0.111 mmol, 25 mg) was added to the flask, and the reaction mixture was stirred at room temperature for 1 hour. TLC showed complete oxidation to dipyromethene. Et3N (0.593 mmol, 0.139 mL) and BF3·OEt2 (0.110 mmol, 0.111 mL) were added to the flask. The addition of both reagents was repeated after 2 minutes, and then the heat block was set to 60°C, and the reaction mixture was stirred at this temperature under argon for 2 hours. Crude BODIPY was directly loaded onto flash silica gel (approximately 25 g). The product was purified by silica gel flash chromatography (80 g, solids content, equilibration 80% DCM / hexane, elution 50% DCM / hexane (2 CV) → 100 DCM / hexane (10 CV) → isocratic 100% DCM / hexane (10 CV) → 0% siRNA / DCM (0 CV) → isocratic 0% siRNA / DCM (5 CV) → 40% siRNA / DCM (40 CV)). The fraction containing the product was evaporated to dryness under vacuum. An orange solid, 50 mg (70% yield) was obtained. MS(APCI):C 54 H 45 Calculated value (M-) for BF5N3O8: 969; Measured value: 969. 11H NMR (400MHz, TCE) δ 8.70(d,J=7.9Hz,1H), 8.65(d,J=8.4Hz,1H), 8.28(d,J=2.2Hz,1H), 8.09( d,J=8.1Hz,1H), 7.85~7.75(m,5H), 7.53(d,J=8.6Hz,1H), 7.40(d,J=8.3Hz ,1H), 6.78(s,2H), 4.67(t,J=6.3Hz,2H), 4.36(t,J=6.4Hz,2H), 4.25(q,J =7.1Hz,4H), 2.81(s,6H), 2.05(s,6H), 1.67(s,6H), 1.32(t,J=7.1Hz,6H).

[0306] Synthesis of compound PLC-19 [ka]

[0307] Compound PLC-19.1 [ka]

[0308] In a flask, PLC-6.3 (1.5 g, 4.1 mmol), 2-(2-aminoethoxy)ethane-1-ol (859.0 mg, 8.2 mmol), and DMAP (35.1 mg, 0.3 mmol) in DMF (30 ml) were degassed at room temperature. The reaction mixture was heated to 165 °C and held at this temperature for 2 hours. TLC and LC-MS indicated completion of the reaction. The reaction mixture was cooled to room temperature. H₂O (70 ml) was added to precipitate the product. The precipitate was collected by filtration. The solid was washed with H₂O (150 ml) and further dried in a vacuum oven at 100 °C for 3 hours to obtain PLC-19.1 as a yellow solid for the next step without further purification. 1.45 g, 78% yield. MS(APCI):C 22 H 16 Calculated value for BrNO5 ([MH] - )=454; Measured value: 454. 1H NMR(400MHz,CDCl2CDCl2) 8.62(d,J=8.0Hz,1H), 8.59(d,J=8.0Hz,1H), 8.19(d,J=2.4Hz,1H), 7.92(d,J=8.0Hz,1H), 7.65(dd,J=8.0Hz,J=2 .4Hz,2H), 7.33(d,J=8.0Hz,1H), 7.29(d,J=8.0Hz,1H), 4.42(t,J=5.6Hz,2H), 3.85(t,J=5.6Hz,2H), 3.67(m,4H).

[0309] Compound PLC-19.2 [ka]

[0310] A stirring bar was attached to a 250 mL flask. PLC-19.1 (800.0 mg, 1.8 mmol), 4-(trifluoromethyl)phenylboronic acid (670.0 mg, 3.5 mmol), Pd(dppf)Cl2 (90.6 mg, 0.1 mmol), and K2CO3 (659.5 mg, 4.8 mmol) were degassed at room temperature from THF / DMF / H2O (48 ml / 9.6 ml / 4.8 ml) in the flask. The reaction mixture was heated to 80 °C and held at this temperature overnight. The reaction was monitored using TLC. After completion, the reaction mixture was work-treated by adding H2O (150 ml) to precipitate the product. The precipitate was collected by filtration. The solid was washed with H2O (200 ml) and MeOH (20 ml), and then dried in a vacuum oven at 100°C for 3 hours. Without further purification, PLC-19.2 was obtained as a yellowish-green solid for the next step. Quantitative yield. MS(APCI):C 29 H 20 Calculated values ​​for F3NO5 ([M+H]) + )=520; Measured value: 520. 1H NMR(400MHz,CDCl2CDCl2) 8.67(d,J=8.0Hz,1H), 8.61(d,J=8.0Hz,1H), 8.26(d,J=2.0Hz,1H), 8.07(d,J=8.0Hz,1H), 7.79(m,5H), 7.52(d ,J=8.4Hz,1H), 7.38(d,J=8.4Hz,1H), 5.11(bs,1H), 4.44(t,J=1.6Hz,2H), 3.86(t,J=1.6Hz,2H), 3.68(m,4H).

[0311] Compounds PLC-19.3A and PLC-19.3B [ka]

[0312] A stirring bar was attached to a 100 mL flask. PLC-19.2 (900.0 mg, 1.7 mmol) and DMF / THF (18 ml / 6 ml) were added to the flask. The solution was degassed at room temperature. Methanesulfonyl chloride (595.4 mg, 5.2 mmol) and TEA (526.2 mg, 5.2 mmol) were added. The solution was then heated to 90°C and held at this temperature for 20 minutes. The reaction was monitored using TLC. After completion, the reaction products were work-treated by adding H2O (150 ml) to precipitate the product. The precipitate was collected by filtration. The solid was washed with H2O (100 ml) and MeOH (15 ml), and further dried in a vacuum oven at 100°C for 3 hours to obtain a mixture of PLC-19.3A and PLC-19.3B as a yellow solid for the next step without further purification. Quantitative yield. For PLC-19.3A, MS(APCI):C 30 H 22 F3NO7S([M+H] + Calculated value = 598; Measured value: 598. 1H NMR (400MHz, CDCl2CDCl2) 8.65(d,J=8.0Hz,1H), 8.60(d,J=8.0Hz,1H), 8.26(d,J=2.0Hz,1H), 8.07(d,J=8.0Hz,1H), 7.78(m,5H), 7.52(d,J=8. 4Hz,1H), 7.38(d,J=8.4Hz,1H), 4.44(t,J=2.0Hz,2H), 4.35(m,2H), 3.86(t,J=2.0Hz,2H), 3.81(m,2H), 3.01(s,3H). PLC-19.3B case, MS (APCI): C 29 H 19 ClF3NO4([MH) - ) Calculated value = 537; Measured value: 537. 1 H NMR (400MHz, CDCl2CDCl2) 8.66(d,J=8.0Hz,1H), 8.61(d,J=8.0Hz,1H), 8.26(d,J=2.0Hz,1H), 8.07(d,J=8.0Hz,1H), 7.79(m,5H), 7.52(d,J=8.4H z,1H), 7.37(d,J=8.4Hz,1H), 4.43(t,J=2.0Hz,2H), 3.86(t,J=2.0Hz,2H), 3.81(t,J=1.6Hz,2H), 3.63(t,J=1.6Hz,2H).

[0313] Compound PLC-19.4

change

[0314] NaH (15.4 mg, 0.4 mmol) and DMF (5 ml) were added to a 100 ml flask, followed by 4-hydroxy-2,6-methylbenzaldehyde (43.6 mg, 0.3 mmol). The mixture was stirred at room temperature for 10 minutes. PLC-19.3B (104.0 mg, 0.2 mmol) was added. The reaction mixture was heated to 160 °C and stirred overnight. TLC (50% ethyl acetate in hexane) indicated completion of the reaction. The reaction mixture was purified by silica gel flash chromatography using ethyl acetate in DCM (0% → 40%) as the eluent to obtain the pure compound PLC-19.4 as an orange solid (73.0 mg, 59% yield). MS(APCI):C 38 H 28 Calculated values ​​for F3NO6 ([M+H]) + )=652; Measured value: 652. 1 H NMR(400MHz,CDCl2CDCl2) δ 10.20(s,1H), 8.61(d,J=8.0Hz,1H), 8.56(d,J=8.0Hz,1H), 8.22(d,J=2.0Hz,1H), 8.00(d,J=8.0Hz,1H), 7.81(m,5H), 7.50(d,J=8 .0Hz,1H), 7.32(d,J=8.0Hz,1H), 6.56(s,2H), 4.44(t,J=2.0Hz,2H), 4.00(m,2H), 3.92(t,J=2.0Hz,2H), 3.86(m,2H), 2.45(s,6H).

[0315] Compound PLC-19 [ka]

[0316] An air condenser and a stirring bar were attached to a 100 mL two-necked round-bottom flask. PLC-19.4 (73.0 mg, 0.1 mmol) and ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (39.0 mg, 0.2 mmol) were added to the flask, followed by anhydrous dichloroethane (7 ml). Ar was sprinkled over the reaction mixture for 30 minutes, followed by the addition of p-TsOH·H2O (0.7 mg, 0.006 mmol). The reaction solution was heated to 85°C and held at this temperature overnight. The reaction mixture was then cooled to room temperature, and DDQ (13.7 mg, 0.06 mmol) was added. The reaction mixture was held at room temperature for 30 minutes. BF3·OEt2 (0.16 mL, 1.3 mmol) and Et3N (0.12 mL, 0.9 mmol) were then added at room temperature. The reaction mixture was heated to 60°C and held at this temperature for 1 hour. The reaction mixture was loaded onto silica gel and purified by flash chromatography using ammonium in DCM (0% → 10%) as an eluent to obtain pure PLC-19 as an orange solid (38.0 mg, 36% yield). MS(APCI):C 56 H 49 Calculated values ​​for BF5N3O9 ([MH] - )=1013; Measured value: 1013. 1 1H NMR (400MHz, CDCl2CDCl2) 8.68(d,J=8.0Hz,1H), 8.63(d,J=8.0Hz,1H), 8.27(d,J=2.4Hz,1H), 8.08( d,J=8.0Hz,1H), 7.79(m,5H), 7.52(d,J=8.0Hz,1H), 7.38(d,J=8.0Hz,1H) , 6.69(s,2H), 4.48(t,J=6.0Hz,2H), 4.26(q,J=7.2Hz,4H), 4.14(m,2H), 3 .92(m,4H), 2.82(s,6H), 2.05(s,6H), 1.70(s,6H), 1.33(t,J=7.2Hz,6H).

[0317] Compound PLC-20 [ka]

[0318] Compound PLC-20.2 [ka]

[0319] PLC-20.1 (1.223 g, 3.33 mmol, 1 equivalent) was suspended in 35 mL of anhydrous DMSO, and 5-amino-1-pentanol (0.687 g, 6.66 mmol, 2 equivalents) was added to the reaction mixture at room temperature. The resulting mixture was stirred at 160 °C for 45 minutes, and LMCMS indicated that the reaction was complete. After cooling to room temperature, the solid was filtered, washed with water (250 mL), then with MeOH (100 mL), and dried in a vacuum oven to obtain 1.2 g of a greenish-yellow solid (85% yield). MS(APCI):C 23 H 18 Calculated value (M-) for BrNO4: 453; Measured value: 453. 1 H NMR(400MHz) δ 8.52(d,J=7.8Hz,1H), 8.48(d,J=8.3Hz,1H), 8.09(d,J=2.3Hz,1H), 7.82(d,J=8.0Hz,1H), 7.54(dd,J=8.8,2.3Hz,1H), 7.23(d,J=8.3Hz,1H) ), 7.19(d,J=8.8Hz,1H), 4.14~4.02(m,2H), 3.64~3.49(m,2H), 1.68(p,J=7.7Hz,2H), 1.60~1.54(m,2H), 1.41(q,J=8.0Hz,2H), 1.28(s,1H).

[0320] Compound PLC-20.3 [ka]

[0321] PLC-20.2 (1.13 g, 2.5 mmol, 1 equivalent) was suspended in DMF (10 ml) and H2O (5 ml), and 4-(trifluoromethyl)benzeneboronic acid (0.949 g, 5.0 mmol, 2 equivalents), K2CO3 (0.691 g, 5.0 mmol, 2 equivalents), and Pd(dppf)Cl2·DCM (40.8 mg, 0.05 mmol, 0.02 equivalents) were added. The mixture was degassed three times by a Vac-Fill argon cycle and heated and stirred at 90°C for 5 hours. The reaction mixture was cooled to room temperature and water was added. The resulting mixture was held at room temperature for 12 hours. The greenish-yellow solid was filtered, washed with water, and then washed with MeOH to obtain 1.24 g of greenish-yellow solid (95% yield). MS(APCI):C 30 H 22 Calculated value (M-) for F3NO4: 517; Measured value: 517. 1 1H NMR (400MHz) δ 8.56(d,J=7.9Hz,1H), 8.51(d,J=8.3Hz,1H), 8.17(d,J=2.1Hz,1H), 7.97( d,J=8.0Hz,1H), 7.69(dd,J=10.3,1.9Hz,4H), 7.42(d,J=8.6Hz,1H), 7.28( d,J=8.3Hz,1H), 4.09(t,J=7.5Hz,2H), 3.57(q,J=6.2Hz,2H), 1.69(p,J=7 .8Hz,2H), 1.61~1.54(m,2H), 1.42(q,J=8.0Hz,2H), 1.28(t,J=5.5Hz,1H).

[0322] Compound PLC-20.4 [ka]

[0323] The mixture of PLC-20.3 (0.66 g, 1.288 mmol) and 48% aqueous HBr (20.0 ml) was refluxed under heat block at 120°C for 5 hours with stirring (HBr 48% bp: 126°C). After cooling to room temperature, the mixture was poured into ice water, the solid was filtered, washed with water, and dried in a vacuum oven to obtain 82% of the desired compound containing unreacted SM. 0.7 g of a greenish-yellow solid (93% yield) was obtained. The product was used in the next step without further purification. MS(APCI):C 30 H 21 Calculated value (M-) for BrF3NO3: 581; Measured value: 581. 1 H NMR(400MHz) δ 8.57(d,J=7.9Hz,1H), 8.51(d,J=8.3Hz,1H), 8.18(d,J=2.2Hz,1H), 7.98(d,J=7.9Hz,1H), 7.69(dd,J=9.6,2.0Hz,4H), 7.43( d,J=8.6Hz,1H), 7.28(d,J=8.3Hz,1H), 4.09(t,J=7.5Hz,3H), 3.38(t,J=6.7Hz,2H), 1.97~1.81(m,2H), 1.69(t,J=7.8Hz,2H).

[0324] Compound PLC-20.5 [ka]

[0325] A mixture of 2,6-dimethyl-4-hydroxybenzaldehyde (60.08 mg, 0.4 mmol, 1 equivalent), K2CO3 (110.56 mg, 0.8 mmol, 2 equivalents), NaI (4.6 mg, catalytic amount), and PLC-20.4 (243.76 mg, 0.42 mmol, 1.05 equivalents) in anhydrous DMF (4.0 ml) was mixed by sonication for 10 minutes before stirring at 65°C under an argon atmosphere for 24 hours. After cooling to room temperature, the mixture was concentrated to dryness, the solid was washed with hot water (50 ml x 2), and the yellow solid was collected by filtration. The crude product was sonicated with MeOH at 65°C, cooled, filtered, and dried in a vacuum oven. The product was used in the next step without further purification, yielding 257 mg in 98% yield. MS(APCI):C 39 H 30 Calculated value (M-) for F3NO5: 649; Measured value: 649. 1 H NMR(400MHz,) δ 10.33(s,1H), 8.56(d,J=7.8Hz,1H), 8.51(d,J=8.4Hz,1H), 8.17(d,J=2.2Hz,1H), 7.98(d,J=8.0Hz,1H), 7.69(dd,J=9.0,1.9Hz,5H), 7.43( d,J=8.6Hz,1H), 7.28(d,J=8.3Hz,1H), 6.51(s,2H), 4.11(t,J=7.6Hz,3H), 3.94(t,J=6.4Hz,2H), 2.50(s,6H), 1.76(dt,J=24.1,7.8Hz,4H).

[0326] Compound PLC-20 [ka]

[0327] Step 1: In a 50 ml vial (equipped with a septum cap and magnetic stirring rod), a mixture of the compounds benzyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (68.55 mg, 0.41 mmol, 2.05 equivalents) and PLC-20.5 (129.93 mg, 0.2 mmol, 1 equivalent) in anhydrous 1,2-dichloroethane (DCE) (4 ml) was bubbling with argon and stirred at room temperature for 15 minutes. Then, a 1 ml mixture of 50 ml DCE + 5 drops of TFA was added all at once. The resulting mixture was then stirred at 68°C for 24 hours under an argon atmosphere. LC-MS showed that only 50% of the starting material was consumed. After adding 8 mg of pTSA and stirring the mixture further at 90°C for 45 minutes, LC-MS showed that the starting material was completely converted. The crude product was used in situ in the next step without further purification.

[0328] Step 2: The above mixture was cooled to room temperature, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (0.148 g, 0.625 mmol) was added all at once. The resulting mixture was stirred at room temperature for 1 / 2 hour. TLC and LCMS showed that the starting materials were completely converted.

[0329] Step 3: The above mixture was cooled to 0°C and then stirred with triethylamine (0.25 ml, 3.48 mmol) for 15 minutes. BF3 etherate (0.71 mL, 2.76 mmol) was added dropwise. The resulting reaction mixture was stirred at 86°C for 45 minutes under an argon atmosphere, cooled to 0°C, quenched with EtOH (2 ml), and the solvent was removed using a rotary evaporator. The residue was subjected to chromatography on a silica gel (80 g) column, eluting only DCM (1 CV), then DCM / siRNA (98:2), and then washed with EtOH to obtain the pure title product (1574-114) as an orange-yellow solid (0.120 g, 59% total yield relative to 1574-112 aldehyde SM). MS(APCI):C 57 H 51 Calculated value (M-) for BF5N3O8: 10¹¹; measured value: 10¹¹. 1H NMR(400MHz,) δ 8.57(d,J=7.9Hz,1H), 8.52(d,J=8.3Hz,1H), 8.17(d,J=2.3Hz,1H), 7.98(d,J=8.0Hz,1H), 7.69(dd,J=9.5,1.8Hz,5H), 7.42(d,J=8.6Hz, 1H), 7.28(d,J=8.3Hz,1H), 6.65(s,2H), 4.18(q,J=7.1Hz,4H), 4.12(t,J=7.6Hz,2H), 3.93(t,J=6.5Hz,2H), 2.73(s,6H), 1.99(s,6H), 1.8 2(t,J=7.3Hz,2H), 1.79~1.69(m,2H), 1.64(s,6H), 1.56(s,2H), 1.24(t,J=7.1Hz,6H). 2.28~2.19(m,4H), 2.06~1.85(m,4H), 0.78(d,J=14.2Hz,2H).

[0330] Compound PLC-21 [ka]

[0331] Compound PLC-21.1 [ka]

[0332] PLC-20.1 (1.223 g, 3.33 mmol, 1 equivalent) was suspended in 35 mL of anhydrous DMSO, and 5-amino-1-pentanol (0.687 g, 6.66 mmol, 2 equivalents) was added to the reaction mixture at room temperature. The resulting mixture was stirred at 160 °C for 3 days, and LMCMS indicated that the reaction was complete. After cooling to room temperature, the solid product was filtered, washed with water (250 mL), then with MeOH (100 mL), and dried in a vacuum oven to obtain 1.2 g of a greenish-yellow solid (92% yield). MS(APCI):C 23 H 18 Calculated value (M-) for BrNO4: 425; Measured value: 425. 1H NMR(400MHz) δ 8.56(d,J=7.9Hz,1H), 8.52(d,J=8.4Hz,1H), 8.13(d,J=2.3Hz,1H), 7.86(d,J=7.9Hz,1H), 7.57(dd,J=8.8,2.3Hz,1H), 7.26( d,J=8.4Hz,1H), 7.22(d,J=8.8Hz,1H), 4.24(t,J=6.1Hz,2H), 3.48(q,J=6.1Hz,2H), 3.06(t,J=6.9Hz,1H), 1.95~1.83(m,2H).

[0333] Compound PLC-21.2 [ka]

[0334] PLC-21.1 (1.06 g, 2.5 mmol, 1 equivalent) was suspended in DMF (10 ml) and H2O (5 ml), and 4-(trifluoromethyl)benzeneboronic acid (0.949 g, 5.0 mmol, 2 equivalents), K2CO3 (0.691 g, 5.0 mmol, 2 equivalents), and Pd(dppf)Cl2·DCM (40.8 mg, 0.05 mmol, 0.02 equivalents) were added. The mixture was degassed three times by a Vac-Fill argon cycle and heated and stirred at 90°C for 5 hours. The reaction mixture was cooled to room temperature and water was added. The resulting mixture was held at room temperature for 12 hours. The greenish-yellow solid was filtered, washed with water, and then washed with MeOH to obtain 1.04 g of greenish-yellow solid (85% yield). MS(APCI):C 30 H 22 Calculated value (M-) for F3NO4: 517; Measured value: 517. 11H NMR (400MHz) δ 8.56(d,J=7.9Hz,1H), 8.51(d,J=8.3Hz,1H), 8.17(d,J=2.1Hz,1H), 7.97( d,J=8.0Hz,1H), 7.69(dd,J=10.3,1.9Hz,4H), 7.42(d,J=8.6Hz,1H), 7.28( d,J=8.3Hz,1H), 4.09(t,J=7.5Hz,2H), 3.57(q,J=6.2Hz,2H), 1.69(p,J=7 .8Hz,2H), 1.61~1.54(m,2H), 1.42(q,J=8.0Hz,2H), 1.28(t,J=5.5Hz,1H).

[0335] Compound PLC-21.3 [ka]

[0336] The mixture of PLC-21.2 (1.6 g, 3.2 mmol) and 48% aqueous HBr (30.0 ml) was heated under reflux at 130°C for 3 days with stirring using a heat block. The same amount of 48% aqueous HBr was added twice more over the next 2 days, for a total volume of 90 ml. After cooling to room temperature, the mixture was poured into ice water, the solid was filtered, washed with water, and dried in a vacuum oven to obtain 82% of the desired compound containing unreacted SM. 1.7 g of a greenish-yellow solid (96% yield) was obtained. The product was used in the next step without further purification. MS(APCI):C 30 H 21 Calculated value (M-) for BrF3NO3: 551; Measured value: 551. 1 H NMR(400MHz) δ 8.55(d,J=7.9Hz,1H), 8.50(d,J=8.4Hz,1H), 8.15(d,J=2.2Hz,1H), 7.96(d,J=8.0Hz,1H), 7.70(s,5H), 7.41 (d,J=8.6Hz,1H), 7.27(d,J=8.3Hz,1H), 4.22(t,J=7.1Hz,2H), 3.45(t,J=6.8Hz,2H), 2.25(q,J=6.9Hz,2H).

[0337] Compound PLC-21.4 [ka]

[0338] A mixture of 2,6-dimethyl-4-hydroxybenzaldehyde (60.08 mg, 0.4 mmol, 1 equivalent), K2CO3 (110.56 mg, 0.8 mmol, 2 equivalents), NaI (4.6 mg, catalytic amount), and PLC-21.3 (231.98 mg, 0.42 mmol, 1.05 equivalents) in anhydrous DMF (4.0 ml) was mixed by sonication for 10 minutes before stirring at 65°C under an argon atmosphere for 24 hours. After cooling to room temperature, the mixture was concentrated to dryness, the solid was washed with hot water (50 ml x 2), and the yellow solid was collected by filtration. The crude material was sonicated with MeOH at 65°C, cooled, filtered, and dried in a vacuum oven. The product was used in the next step without further purification, yielding 239 mg in 96% yield. MS(APCI):C 37 H 26 Calculated value (M-) for F3NO5: 621; Measured value: 621. 1 H NMR(400MHz,) δ 10.34(s,1H), 8.56(d,J=7.7Hz,1H), 8.51(d,J=8.3Hz,1H), 8.18(d,J=2.2Hz,1H), 7.98(d,J=7.9Hz,1H), 7.70(dd,J=7.4,2.3Hz,6H),7. 44(d,J=8.6Hz,1H), 7.29(d,J=8.2Hz,1H), 6.46(s,2H), 4.30(t,J=7.0Hz,2H), 4.09(t,J=5.9Hz,2H), 2.47(s,6H), 2.17(t,J=6.7Hz,2H).

[0339] Compound PLC-21 [ka]

[0340] Step 1: In a 50 ml vial (equipped with a septum cap and magnetic stirrer), a mixture of compounds benzyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (68.55 mg, 0.41 mmol, 2.05 equivalents) and PLC-21.4 (124.32 mg, 0.2 mmol, 1 equivalent) in anhydrous 1,2-dichloroethane (DCE) (4 ml) was bubbling with argon and stirred at room temperature for 15 minutes. Then, a 1 ml mixture of 50 ml DCE + 5 drops of TFA was added all at once. The resulting mixture was then stirred at 68°C for 24 hours under an argon atmosphere, and LCMS showed that only 50% of the starting material had been consumed. 8 mg of pTSA was added, and the mixture was further stirred at 90°C for 45 minutes, and LCMS showed that the starting material had been completely converted. The crude product was used in the next step in situ without further purification.

[0341] Step 2: The above mixture was cooled to room temperature, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (0.148 g, 0.625 mmol) was added all at once. The resulting mixture was stirred at room temperature for 1 / 2 hour. TLC and LCMS showed that the starting materials were completely converted.

[0342] Step 3: The above mixture was cooled to 0°C and then stirred with triethylamine (0.25 ml, 3.48 mmol) for 15 minutes. BF3 etherate (0.71 mL, 2.76 mmol) was added dropwise. The resulting reaction mixture was stirred at 86°C for 45 minutes under an argon atmosphere, cooled to 0°C, quenched with EtOH (2 ml), and the solvent was removed using a rotary evaporator. The residue was subjected to chromatography on a silica gel (80 g) column, eluting only DCM (1 CV), then DCM / siRNA (98:2), and then washed with EtOH to obtain the pure title product PLC-21 as an orange-yellow solid (0.097 g, 49% total yield relative to PLC-21 aldehyde SM). MS(APCI):C 55 H 47 Calculated value (M-) for BF5N3O8: 983; Measured value: 983. 1H NMR(400MHz,) δ 8.56(d,J=7.9Hz,1H), 8.51(d,J=8.3Hz,1H), 8.17(d,J=2.1Hz,1H), 7.98(d,J=8.0 Hz,1H), 7.69(dd,J=8.8,2.0Hz,5H), 7.42(d,J=8.6Hz,1H), 7.28(d,J=8.3Hz,1H), 6.58(s,2H), 4.33(t,J=7.1Hz,2H), 4.18(q,J=7.1Hz,4H), 4.08(t,J=6.2Hz,2H), 2 .73(s,6H), 2.19(t,J=6.8Hz,2H), 1.63(s,6H), 1.53(s,8H), 1.25(t,J=7.1Hz,6H).

[0343] Synthesis of compound PLC-22 [ka]

[0344] Compound PLC-22.1: A mixture of compound PLC-27.1 (see above) (9-bromo-2-(3-hydroxypropyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione) (330 mg, 0.778 mmol), (2,4,6-triisopropylphenyl)boronic acid (290 mg, 1.17 mmol), Pd(PPh3)4 (80 mg, 0.069 mmol), and K2CO3 (320 mg, 2.32 mmol) in 1,4-dioxane / DMF / water (15 mL / 3 mL / 1.5 mL) was degassed and heated at 90 °C for 24 hours. The resulting mixture was post-treated with water and ethyl acetate. The organic phase was collected, loaded onto silica gel, and purified by flash chromatography using DCM / EA (0% → 40% EA) as the eluent. After removing the solvent under reduced pressure, the desired fraction was collected to obtain a yellow solid (210 mg, 49% yield). LC-MS(APCI-):C 36 H 37 Calculated value for NO4 = 547.27; Measured value: 547. 1H NMR(400MHz,d2-TCE) δ 8.60~8.48(m,2H), 7.93~7.76(m,2H), 7.45~7.24(m,3H), 6.99(s,2H), 4.25(t,J=6.1Hz,2H), 4.01(q,J=7.2Hz,2H), 3.47(t, J=5.5Hz,2H), 2.88(p,J=6.8Hz,1H), 2.65~2.43(m,2H), 1.89(d,J=6.2Hz,2H), 1.24(d,J=6.9Hz,6H), 1.03(t,J=7.1Hz,12H).

[0345] Compound PLC-22.2: To a solution of compound 1612-48 (210 mg, 0.384 mmol) in 20 mL of DCM, carbon tetrabromide (CBr4, 252 mg, 0.76 mmol) and triphenylphosphine (203 mg, 0.77 mmol) were added at room temperature. The mixture was stirred for 30 minutes. TLC indicated that the reaction was complete. The mixture was loaded onto silica gel and purified by flash chromatography using hexane / DCM (0% → 100% DCM) as the eluent. The desired fraction was collected and concentrated under reduced pressure to obtain a yellow solid (100 mg, 43% yield). LCMS(APCI+):C 36 H 37 Calculated value (M+H) for BrNO3: 610.19; Measured value: 610. 1 H NMR(400MHz,d2-TCE) δ 8.52(dd,J=8.1,2.5Hz,2H), 8.00~7.72(m,2H), 7.45~7.19(m,3H), 6.98(s,2H), 4.23(t,J=7.0Hz,2H), 3.44(t,J=6. 8Hz,2H), 3.01~2.80(m,1H), 2.69~2.45(m,2H), 2.26(q,J=6.9Hz,2H), 1.24(d,J=6.9Hz,6H), 1.03(t,J=6.9Hz,12H).

[0346] Compound PLC-22: A mixture of compound PLC-22.1 (50 mg, 0.082 mmol), compound PLC1.1 (58.5 mg, 0.10 mmol), and K2CO3 (20.7 mg, 0.15 mmol) in anhydrous DMF was sonicated for 3 minutes and then heated at 75°C for 5 hours under an argon atmosphere. The resulting mixture was diluted with 100 mL of DCM, washed with 0.1 N aqueous HCl (50 mL x 2), dried over MgSO4, concentrated to 50 mL, then loaded onto silica gel, and purified by flash chromatography using DCM / EA (0% → 5% EA) as the eluent. The main desired fraction was collected, concentrated, triturated with methanol, and subsequently filtered to obtain a dark red solid (70 mg, 76.6% yield). LCMS(APCI-):C 69 H 60 Calculated value for BCl2F2N3O4: 1113.40; Measured value: 1113. 1 H NMR(400MHz,d2-TCE) δ 8.63~8.43(m,2H), 8.08~7.72(m,4H), 7.46~7.13(m,9H), 6.94(d,J=31.3Hz,4H), 6.38(s,2H), 4.35(t,J=6.8Hz,2H), 4.12(t,J=5.9Hz,2H) ), 2.98~2.77(m,1H), 2.54(q,J=6.8Hz,6H), 2.23(d,J=6.0Hz,6H), 2.04~1.89(m,4H), 1.23(d,J=6.9Hz,6H), 1.02(dd,J=6.9,3.5Hz,12H).

[0347] Synthesis of compound PLC-23 [ka]

[0348] Compound PLC-23.2 4-(3-(9-(3,5-bis(trifluoromethyl)phenyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propoxy)-2,6-dimethylbenzaldehyde A mixture of 2,6-dimethyl-4-hydroxybenzaldehyde (30.04 mg, 0.4 mmol, 1 equivalent), K2CO3 (55.28 mg, 0.4 mmol, 2 equivalents), NaI (2.3 mg, catalytic amount), and PLC-23.1 (130.2735 mg, 0.21 mmol, 1.05 equivalents) in anhydrous DMF (4.0 ml) was mixed by sonication for 10 minutes before stirring at 65°C under an argon atmosphere for 24 hours. After cooling to room temperature, the mixture was concentrated to dryness. The residue was washed with hot water (50 ml x 2), and the yellow solid was collected by filtration. The solid was then sonicated with MeOH at 65°C, cooled, filtered, dried in a vacuum oven, and used in the next step without further purification of the product, yielding 135 mg in 85% yield. MS(APCI): Chemical formula: C 38 H 25 Calculated value (M-) for F6NO5: 689; measured value: 689. 1 H NMR(400MHz) δ 10.34(s,1H), 8.57(d,J=7.9Hz,1H), 8.52(d,J=8.3Hz,1H), 8.16(d,J=2.2Hz,1H), 8.02(d,J=8.9Hz,2H), 7.86(s,1H), 7.70(dd,J=8.6,2 .1Hz,1H), 7.47(d,J=8.6Hz,1H), 7.30(d,J=8.3Hz,1H), 6.46(s,2H), 4.30(t,J=7.1Hz,2H), 4.09(t,J=6.0Hz,2H), 2.47(s,3H), 2.18(t,J =6.6Hz,2H).

[0349] Compound PLC-23: Diethyl 10-(4-(3-(9-(3,5-bis(trifluoromethyl)phenyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)yl)-propoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l 4 ,5l 4 -Dipyrololo[1,2-c:2',1'-f][1,3,2]diazavorinine-2,8-carboxylate

[0350] Step 1: In a 50 ml vial (equipped with a septum cap and magnetic stirring rod), a mixture of compounds benzyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (58.19 mg, 0.348 mmol, 2.1 equivalents) and 1643-005 (115 mg, 0.166 mmol, 1 equivalent) in anhydrous 1,2-dichloroethane (DCE) (4 ml) was bubbling with argon and stirred at room temperature for 15 minutes. 8 mg of pTSA was added, and the mixture was stirred at 85°C for 45 minutes. LC-MS showed that the starting materials were completely converted. The crude product was used in the next step in situ without further purification.

[0351] Step 2: The above mixture was cooled to room temperature, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (0.113 g, 0.498 mmol, 3 equivalents) was added all at once. The resulting mixture was stirred at room temperature for 1 / 2 hour. TLC and LCMS showed that the starting materials were completely converted.

[0352] Step 3: The above mixture was cooled to 0°C and then stirred with triethylamine (0.462 ml, 3.48 mmol, 3.32 mmol, 20 equivalents) for 15 minutes. BF3 etherate (1.224 mL, 9.96 mmol, 60 equivalents) was added dropwise. The resulting reaction mixture was sonicated under an argon atmosphere at room temperature for 10 minutes, then stirred at 60°C for 45 minutes, and then stirred at room temperature for 16 hours. After quenching with EtOH (2 ml), the reaction mixture was concentrated using a rotary evaporator. The residue was washed with hot water, and the crude product was subjected to chromatography on a silica gel (80 g) column, eluting only DCM (1 CV), then DCM / siRNA (98:2), and then washed with EtOH to obtain the pure title product (1643-006) as an orange-yellow solid (105 mg, 60% total yield based on 1643-005 aldehyde SM). MS(APCI):Chemical formula:C 56 H 46 Calculated value (M-) for BF8N3O8: 689 1051; Measured value: 1051. 1H NMR(400MHz) δ 8.59(d,J=7.8Hz,1H), 8.52(d,J=8.3Hz,1H), 8.17(d,J=2.2Hz,1H), 8.03(d,J=8.1Hz,1H), 8.00(d,J=1.5Hz,2H), 7.86(s,1H), 7.69(dd ,J=8.6,2.2Hz,1H), 7.46(d,J=8.6Hz,1H), 7.30(d,J=8.3Hz,1H), 6.59(s,2H), 4.34(t,J=7.1Hz,2H), 4.18(q,J=7.1Hz,4H), 4.08(t,J= 6.2Hz,2H), 2.73(s,6H), 2.25~2.13(m,2H), 1.95(s,6H), 1.63(s,6H), 1.25(t,J=7.1Hz,6H).

[0353] Synthesis of compound PLC-24

change

[0354] Compound PLC-24.1:4'-(tert-ブチル)-3-ニトロ-[1,1'-ビフェニル]-4-オール 4-Bromo-2-nitrophenol (5.45 g, 25.0 mmol) and 4-(t-butyl)benzeneboronic acid (5.563 g, 31.25 mmol) were dissolved in dioxane (100 mL) at room temperature and stirred for 5 minutes. After a clear solution was formed, Pd(PPh3)2Cl2 (0.175 g, 0.25 mmol) and 4N K2CO3 aqueous solution (25.0 ml, 50 mmol, 2 equivalents) were rapidly added, and the mixture was degassed three times using a Vac-Fil nitrogen cycle, followed by heating at 80°C for 4 hours. After the reaction mixture cooled to room temperature, the pH was adjusted to 5-6 with 4N HCl aqueous solution, extracted with ethyl acetate (250 mL), and passed through a short Celite pad. The pad was washed with EA (150 ml x 2). The organic layers were combined, washed with brine (25 mL), dried over anhydrous MgSO4, and concentrated under reduced pressure. The residue was dissolved in Hex:EA(95:5) (150 ml), and the dark solid was filtered off by filtration through a short pad of Celite. The filtrate was concentrated to obtain a yellow solid, which was then triturated with hexane to obtain a yellow solid of 3.8 (56% yield). MS(APCI): Chemical formula: C 16 H 17 Calculated value (M-) for NO3: 271; Measured value: 271. 1 ¹H NMR (400MHz, chloroform-d) δ 10.57 (s, 1H), 8.32 (d, J=2.3Hz, 1H), 7.83 (dd, J=8.7, 2.4Hz, 1H), 7.50 (d, J=1.5Hz, 4H), 7.23 (d, J=8.7Hz, 1H), 1.37 (s, 9H).

[0355] Compound PLC-24.2:6-((4'-(tert-butyl)-3-nitro-[1,1'-biphenyl]-4-yl)oxy)-1H,3H-benzo[de]isochromen-1,3-dione 4-bromonaphthalic anhydride (10 g, 36 mmol, 1.15 equivalents), 4'-(tert-butyl)-3-nitro-[1,1'-biphenyl]-4-ol (1574-71) (8.5 g, 31.32 mmol, 1 equivalent), and NaOH (0.864 g, 21.6 mmol, 0.6 equivalents) were mixed in anhydrous NMP (65 mL), copper powder (1.371 g, 21.6 mmol, 0.6 equivalents) was added, and the resulting mixture was degassed three times using a Vac-Fil nitrogen cycle. Then, under an N2 atmosphere, it was heated and stirred at 145°C for 5 hours, followed by heating overnight at room temperature. The RX mixture was post-treated with an aqueous HCl solution and left at room temperature for 12 hours to precipitate the brown solid. The mixture was filtered and washed with hot MeOH (250 ml x 3) to obtain a light brown solid (10.8 g, 23.1 mmol) (73% yield, 86% purity). MS(APCI): Chemical formula: C 28 H 21 Calculated value (M-) for NO6: 467; Measured value: 467.

[0356] Compound PLC-24.3:6-((3-amino-4'-(tert-butyl)-[1,1'-biphenyl]-4-yl)oxy)-1H,3H-benzo[de]isochromen-1,3-dione To a mixture of compound PLC-24.2 (4.885 g, 10.45 mmol, 1.0 equivalent) in 2-MeTHF (70.0 mL) and HCl (4 M, 26.1 mL, 10 equivalents), SnCl2·2H2O (9.4 g, 41.75 mmol, 4.0 equivalents) was added all at once. The mixture was stirred at 90°C for 1 / 2 hour. TLC (hexane / ethyl acetate = 7:3) and LCMS indicated that the reaction was complete. The white solid was filtered off and washed with EA / 2-MeTHF (1:1) (100 mL x 2). The combined organic filtrate was washed with water, separated, and concentrated under reduced pressure to obtain a viscous solid residue. The crude product was washed with 100 mL of hot water at 50°C for 1 / 2 hour, filtered, and then dried under reduced pressure to obtain 1574-78 (4.5 g, 10.28 mmol) as a yellowish-brown solid (98% yield). MS(APCI): Chemical formula: C 28 H 23 Calculated value (M-) for NO4: 437; Measured value: 437

[0357] Compound PLC-24.4:9-(4-(tert-butyl)phenyl)-1H,3H-isochromeno[6,5,4-mna]xanthene-1,3-dione Compound PLC-24.3 (1.844 g, 4.215 mmol, 1.0 equivalent) in AcOH (28.5 mL) and H2O (9.0 mL) was added dropwise to concentrated HCl (2.445 mL) and NaNO2 (2.9 g, 42.15 mmol, 10 equivalents) in H2O (9 mL), and the mixture was stirred at 0°C for 1 hour. The above solution was added to CuSO45H2O (4.35 g, 17.42 mmol, 4.1 equivalents) in H2O (175 mL) and AcOH (11 mL) over 1 / 2 hour at 130°C via a dropping funnel. After the addition was complete, the resulting mixture was stirred for a further 15 minutes at the same temperature of 130°C. The mixture was filtered and washed with H2O (3 × 100 mL). → 0.445 g of the crude product was triturated with EtOH. →0.42g of pure compound, 30% yield. MS(APCI): Chemical formula: C 28 H 20 Calculated value (M-) for O4: 420; Measured value: 420.

[0358] Compound PLC-24.5:9-(4-(tert-butyl)phenyl)-2-(3-hydroxypropyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione Compound PLC-24.4 (0.420 g, 1.0 mmol, 1.0 equivalent) in anhydrous DMSO (4 mL) was added to 3-amino-1-propanol (0.300 g, 4.0 mmol, 4.0 equivalent) at room temperature, and the resulting mixture was stirred at 130°C for 45 minutes. After the reaction was complete, DMSO was removed by filtration. The solid was washed with water (50 ml x 3) and dried in a vacuum oven to obtain 0.45 g of yellow solid (94% yield). MS(APCI): Chemical formula: C 31 H 27 Calculated value (M-) for NO4: 477; Measured value: 477. 1H NMR(400MHz,chloroform-d) δ 10.44(s,2H), 8.65(d,J=7.8Hz,1H), 8.60(d,J=8.3Hz,1H), 8.25(d,J=2.0Hz,1H ), 8.03(d,J=8.0Hz,1H), 7.76(dd,J=8.6,2.1Hz,1H), 7.61(d,J=8.3Hz,2H), 7.54 (d,J=8.2Hz,2H), 7.45(d,J=8.6Hz,1H), 7.32(d,J=8.3Hz,1H), 6.50(s,2H), 4.4 2(t,J=6.9Hz,2H), 4.17(t,J=6.2Hz,2H), 2.54(s,6H), 2.28(s,2H), 1.40(s,9H).

[0359] Compound PLC-24.6: 2-(3-bromopropyl)-9-(4-(tert-butyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione A mixture of compound 24.5 (0.453 g, 0.95 mmol) and 48% aqueous HBr (20 ml) was stirred and heated in a heat block at 130°C for 8 hours. LC-MS showed that the SM was completely consumed. The mixture was cooled to room temperature and left to stand at room temperature for 16 hours. The yellow solid was filtered, washed several times with water, and dried in a vacuum oven to obtain 0.275 g in 96% yield. The product was used in the next step without further purification. MS (APCI): Chemical formula: C 31 H 26 Calculated value (M-) for BrNO3: 540; Measured value: 540. 1 H NMR(400MHz) δ 8.59(d,J=7.8Hz,1H), 8.53(d,J=8.4Hz,1H), 8.19(s,1H), 7.99(d,J=8.0Hz,1H), 7.72(d,J=8.7Hz,1H), 7.55(d,J=8.0Hz,2H), 7.45(d,J=8. 0Hz,2H), 7.41(d,J=8.5Hz,1H), 7.29(d,J=8.4Hz,1H), 4.25(s,2H), 3.48(d,J=6.1Hz,2H), 3.16(d,J=6.8Hz,1H), 1.90(s,2H), 1.31(s,9H).

[0360] Compound PLC-24.7: 4-(3-(9-(4-(tert-butyl)phenyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propoxy)-2,6-dimethylbenzaldehyde A mixture of 2,6-dichloro-4-hydroxybenzaldehyde (Combi Block, cas#60964-09-2), QF-6704 (batch 31758, 95% purity) (32 mg, 0.159 mmol, 1 equivalent), K2CO3 (32.5 mg, 0.23.5 mmol, 1.47 equivalents), NaI (2.3 mg, catalytic amount), and 1643-011 (96.74 mg, 0.179 mmol, 1.125 equivalents) in anhydrous DMF (1.0 ml) was mixed by sonication for 10 minutes before stirring at 85°C for 4 hours under an argon atmosphere. LCMS showed only 10% conversion. The mixture was then heated and stirred to 65°C for 5 hours. After cooling to room temperature, the mixture was concentrated to dryness, the solid was washed with hot water (50 ml x 2), the yellow solid was collected by filtration, then sonicated with MeOH at room temperature, filtered, dried in a vacuum oven, and the product was used in the next step without further purification to obtain 27.0 mg of 1643-015 (75% yield). MS(APCI): Chemical formula: C 40 H 35 Calculated value (M-) for NO5: 609; Measured value: 609. 1 H NMR(400MHz,chloroform-d) δ 10.44(s,2H), 8.65(d,J=7.8Hz,1H), 8.60(d,J=8.3Hz,1H), 8.25(d,J=2.0Hz,1H ), 8.03(d,J=8.0Hz,1H), 7.76(dd,J=8.6,2.1Hz,1H), 7.61(d,J=8.3Hz,2H), 7.54 (d,J=8.2Hz,2H), 7.45(d,J=8.6Hz,1H), 7.32(d,J=8.3Hz,1H), 6.50(s,2H), 4.4 2(t,J=6.9Hz,2H), 4.17(t,J=6.2Hz,2H), 2.54(s,6H), 2.28(s,2H), 1.40(s,9H).

[0361] Compound PLC-24: Diethyl 10-(4-(3-(9-(4-(tert-butyl)phenyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate

[0362] Step 1: In a 50 ml vial (equipped with a septum cap and magnetic stirring rod), a mixture of compound 1643-015 (68.28 mg, 0.112 mmol, 1 equivalent) and ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (38.4 mg, 0.23 mmol, 2.05 equivalents) in anhydrous 1,2-dichloroethane (DCE) (2 ml) was bubbling with argon, stirred at room temperature for 15 minutes, 4 mg of pTSA was added, and the mixture was further stirred at 86°C for 45 minutes. LC-MS showed that the starting materials had been completely converted. The crude product was used in the next step in situ without further purification.

[0363] Step 2: The above mixture was cooled to room temperature, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (79.45 mg, 0.35 mmol) was added all at once. The resulting mixture was stirred at room temperature for 1 / 2 hour. TLC and LCMS showed that the starting materials were completely converted.

[0364] Step 3: The above mixture was cooled to 0°C and then stirred with triethylamine (0.125 ml, 1.74 mmol) for 15 minutes. BF3 etherate (0.71 mL, 2.76 mmol) was added dropwise. The resulting reaction mixture was stirred at 86°C for 45 minutes under an argon atmosphere, cooled to 0°C, quenched with EtOH (2 ml), and the solvent was removed using a rotary evaporator. The residue was subjected to chromatography on a silica gel (80 g) column, eluting only DCM (1 CV), then DCM / siRNA (98:2), and then washed with EtOH to obtain the pure title product (1643-017) as an orange-yellow solid (40 mg, 36% total yield relative to aldehyde SM of 1643-015). MS (APCI): Chemical formula: C 58 H 56 Calculated value (M-) for BF2N3O8: 971; measured value: 971. 1 H NMR(400MHz,chloroform-d) δ 8.65(d,J=7.8Hz,1H), 8.60(d,J=8.3Hz,1H), 8.24(d,J=2.1Hz,1H), 8.03(d,J=8.0Hz,1H), 7.75(dd ,J=8.6,2.1Hz,1H), 7.61(d,J=8.4Hz,2H), 7.56~7.49(m,2H), 7.44(d,J=8.6Hz,1H), 7.32(d,J=8.4H) z,1H), 6.64(s,2H), 4.45(t,J=6.9Hz,2H), 4.28(q,J=7.1Hz,4H), 4.15(t,J=6.3Hz,2H),2.83(s,6H) ), 2.30(t,J=6.7Hz,2H), 2.02(s,6H), 1.71(s,6H), 1.56(s,6H), 1.40(s,9H), 1.33(t,J=7.1Hz,6H).

[0365] Synthesis of PLC-25 [ka]

[0366] Compound PLC-25.1:9-bromo-2-(4-hydroxybutyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione A stirring bar was attached to a 100 mL flask. Compound PLC-3.3 (1.0 g, 2.7 mmol), 4-aminobutan-1-ol (485.3 mg, 5.4 mmol), and DMAP (23.1 mg, 0.19 mmol) in DMF (20 ml) were degassed at room temperature into the flask. The reaction mixture was heated to 165 °C and held at this temperature for 2.5 hours. TLC and LC-MS indicated completion of the reaction. The reaction mixture was cooled to room temperature. H₂O (80 ml) was added. The solid product was collected by vacuum filtration, washed with H₂O (100 ml), and further dried in a vacuum oven at 100 °C for 3 hours. Compound PLC-25.1 was obtained as a brown solid for the next step without further purification. 908.0 mg, 77% yield. MS (APCI): Chemical formula: C 22 H 16 Calculated value for BrNO4 ([MH] - )=438; Measured value: 438. 1 H NMR(400MHz,CDCl2CDCl2) 8.62(d,J=8.0Hz,1H), 8.58(d,J=8.0Hz,1H), 8.19(d,J=2.4Hz,1H), 7.93(d,J=8.0Hz,1H), 7.64(dd,J=8.0Hz,J=2.4Hz,2 H), 7.32(d,J=8.0Hz,1H), 7.28(d,J=8.0Hz,1H), 4.20(t,J=7.2Hz,2H), 3.83(t,J=6.0Hz,2H), 1.82(m,2H), 1.69(m,2H).

[0367] Compound PLC-25.2: 2-(4-hydroxybutyl)-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione A stirring bar was attached to a 250 mL flask. Compound PLC-25.1 (900.0 mg, 2.1 mmol), 4-(trifluoromethyl)phenylboronic acid (780.0 mg, 4.1 mmol), Pd(dppf)Cl2 (107.5 mg, 0.15 mmol), and K2CO3 (782.5 mg, 5.7 mmol) were degassed at room temperature from THF / DMF / H2O (60 ml / 12 ml / 6 ml) into the flask. The reaction mixture was heated to 80 °C and the reaction product was held at this temperature overnight. The reaction was monitored using TLC. After completion, the reaction product was work-treated by adding H2O (150 ml) to precipitate the product. The precipitate was collected by filtration. The solid was washed with H2O (200 ml) and MeOH (20 ml), and then dried in a vacuum oven at 100°C for 3 hours. Without further purification, compound 25.2 was obtained as a yellow solid for the next step. 990.0 mg, 94% yield. MS (APCI): Chemical formula: C 29 H 20 Calculated values ​​for F3NO4 ([M+H]) + )=504; Measured value: 504. 1 H NMR(400MHz,CDCl2CDCl2) 8.67(d,J=8.0Hz,1H), 8.61(d,J=8.0Hz,1H), 8.27(d,J=2.4Hz,1H), 8.08(d,J=8.0Hz,1H), 7.80(m,5H), 7.52(d,J=8.4Hz,1H), 7.38(d,J=8.4Hz,1H), 4.22(t,J=7.2Hz,2H), 3.73(t,J=6.0Hz,2H), 1.84(m,4H).

[0368] Compound PLC-25.3: 4-(1,3-dioxo-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)butyl 4-methylbenzene sulfonate A stirring bar was attached to a 100 mL flask. Compound PLC-25.2 (200.0 mg, 0.40 mmol) and DCE (20 ml) were added to the flask. The solution was degassed at room temperature, and p-toluenesulfonic anhydride (519.0 mg, 1.6 mmol) and TEA (221.0 μL, 1.6 mmol) were added. The solution was then heated to 90 °C and maintained at this temperature for 4 hours. The reaction was monitored using TLC and LC-MS. Further additions of DCE (20 mL) and p-toluenesulfonic anhydride (519.0 mg, 1.6 mmol) were added. The reaction mixture was cooled to room temperature. H2O (100 ml) and TEA (221.0 μL, 1.6 mmol) were added. The reaction mixture was maintained at 90 °C overnight. The mixture was stopped by adding H2O (150 ml), and then extracted with DCM (150 ml x 3). The combined organic phase was dried with anhydrous Na2SO4 and concentrated under a vacuum rotary evaporator to obtain compound PLC-25.3 as a yellow solid, which was used in the next step without further purification. MS(APCI): Chemical formula: C 36 H 26 Calculated values ​​for F3NO6S ([MH]) - )=657; Measured value: 657. 1 H NMR(400MHz,CDCl3)8.55(d,J=8.0Hz,1H), 8.51(d,J=8.0Hz,1H), 8.16(d,J=2.0Hz,1H), 7.92(d,J=8.0Hz,1H), 7.76 (m,7H), 7.41(d,J=8.4Hz,1H), 7.32(d,J=8.0Hz,2H), 7.24(d,J=8.0Hz,1H), 4.10(m,4H), 2.42(s,3H), 1.76(m,4H).

[0369] Compound PLC-25.4: 4-(4-(1,3-dioxo-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)butoxy)-2,6-dimethylbenzaldehyde Compound PLC-25.3 (131.5 mg, 0.20 mmol) and 4-hydroxy-2,6-methylbenzaldehyde (33.0 mg, 0.22 mmol) in DMF (5 mL) were added to a 25 ml vial. The solution was degassed at room temperature, and K2CO3 (41.4 mg, 0.30 mmol) was added. The reaction mixture was further degassed at room temperature. The mixture was then heated to 65 °C and stirred overnight. TLC (50%  in hexane) indicated completion of the reaction. The reaction mixture was purified by silica gel flash chromatography using  in hexane (0% → 40% → 60%) as the eluent to obtain pure compound PLC-25.4 as a solid (30.0 mg, 24% yield (over two steps)). MS (APCI): Chemical formula: C 38 H 28 Calculated values ​​for F3NO5 ([MH] - )=635; Measured value: 635. 1 H NMR(400MHz,CDCl3) δ 10.43(s,1H), 8.64(d,J=8.0Hz,1H), 8.60(d,J=8.0Hz,1H), 8.23(d,J=2.4Hz,1H), 8.02(d,J=8.0Hz,1H), 7.77(s,4H), 7.74(dd,J=8.0Hz,2. 0Hz,1H), 7.47(d,J=8.0Hz,1H), 7.31(d,J=8.0Hz,1H), 6.56(s,2H), 4.28(t,J=6.8Hz,2H), 4.07(t,J=6.0Hz,2H), 1.94(m,6H), 1.58(m,4H).

[0370] Compound PLC-25: Diethyl 10-(4-(4-(1,3-dioxo-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-butoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate An air condenser and stirring bar were attached to a 100 mL two-necked round-bottom flask. Compound 25.4 (67.0 mg, 0.1 mmol) and ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (37.0 mg, 0.2 mmol) were added to the flask, followed by anhydrous dichloroethane (7 ml). Ar was sprinkled over the reaction mixture for 30 minutes, followed by the addition of p-TsOH·H2O (0.67 mg, 0.006 mmol). The reaction solution was heated to 85 °C and held at this temperature overnight. The reaction mixture was then cooled to room temperature and DDQ (13.7 mg, 0.06 mmol) was added. The reaction mixture was held at room temperature for 30 minutes. BF3·OEt2 (0.16 mL, 1.3 mmol) and Et3N (0.12 mL, 0.9 mmol) were then added at room temperature. The reaction mixture was heated to 60 °C and held at this temperature for 1 hour. At room temperature, BF3·OEt2 (0.16 mL, 1.3 mmol) and Et3N (0.12 mL, 0.9 mmol) were added. The reaction mixture was heated to 60°C and held at this temperature for 3 hours. The reaction mixture was loaded onto silica gel and purified by flash chromatography using siRNA in DCM (0% → 10% → 14%) as an eluent to obtain pure compound PLC-25 as an orange solid (12.0 mg, 11% yield). MS (APCI): Chemical formula: C 56 H 49 Calculated values ​​for BF5N3O8 ([MH] - )=997; Measured value: 997. 1 H NMR(400MHz,CDCl2CDCl2)8.68(d,J=8.0Hz,1H), 8.62(d,J=8.0Hz,1H), 8.28(d,J=2.0Hz,1H), 8.09(d,J=8.0Hz,1H), 7.79(m,5H), 7.52(d,J=8.0 Hz,1H), 7.39(d,J=8.0Hz,1H), 6.75(s,2H), 4.27(m,6H), 4.07(m,2H), 2. 82(s,6H), 2.07(s,6H), 1.97(m,4H), 1.72(s,6H), 1.33(t,J=7.2Hz,6H).

[0371] Synthesis of compound PLC-26 [ka]

[0372] Compound PLC-26.2: 4-(2-(2-(2-(1,3-dioxo-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)ethoxy)ethoxy)ethoxy)-2,6-dimethylbenzaldehyde Compound PLC-26.1 (186.6 mg, 0.26 mmol) and 4-hydroxy-2,6-methylbenzaldehyde (43.0 mg, 0.29 mmol) in DMF (5 mL) were added to a 25 ml vial. The solution was degassed at room temperature, and K2CO3 (53.8 mg, 0.39 mmol) was added. The reaction mixture was further degassed at room temperature. The mixture was then heated to 65 °C and stirred overnight. TLC (50%  in hexane) indicated completion of the reaction. The reaction mixture was purified by silica gel flash chromatography using  in hexane (0% → 40% → 60%) as the eluent to obtain pure compound PLC-26.2 as a yellow solid (70.0 mg, 39% yield (over two steps)). MS (APCI): Chemical formula: C 40 H 32 Calculated values ​​for F3NO7 ([MH] - )=695; Measured value: 695. 1 1H NMR (400MHz, CDCl2CDCl2) δ 10.30(s,1H), 8.58(d,J=8.0Hz,1H), 8.54(d,J=8.0Hz,1H), 8.16(d,J=2.0H z,1H), 7.95(d,J=8.0Hz,1H), 7.79(s,4H), 7.75(dd,J=8.0Hz,2.0Hz,1H), 7 .44(d,J=8.0Hz,1H), 7.28(d,J=8.0Hz,1H), 6.40(s,2H), 4.43(t,J=6.0Hz, 2H), 3.90(t,J=4.4Hz,2H), 3.84(t,J=6.0Hz,2H), 3.72(m,6H), 2.48(s,6H).

[0373] Compound PLC-26: Diethyl 10-(4-(2-(2-(2-(1,3-dioxo-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)ethoxy)ethoxy)ethoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate An air condenser and stirring bar were attached to a 100 mL two-necked round-bottom flask. Compound PLC-26.2 (70.0 mg, 0.1 mmol) and ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (35.3 mg, 0.2 mmol) were added to the flask, followed by anhydrous dichloroethane (5 ml). Ar was sprinkled over the reaction mixture for 30 minutes, and then p-TsOH·H2O (3.7 mg, 0.03 mmol) was added. The reaction solution was heated to 65 °C and held at this temperature overnight. The reaction mixture was then cooled to room temperature and DDQ (12.4 mg, 0.06 mmol) was added. The reaction mixture was held at room temperature for 30 minutes. BF3·OEt2 (0.15 mL, 1.2 mmol) and Et3N (0.11 mL, 0.8 mmol) were then added at room temperature. The reaction mixture was heated to 60 °C and held at this temperature for 1 hour. The reaction mixture was loaded onto silica gel and purified by flash chromatography using toluene in DCM (0% → 10%) as an eluent to obtain pure compound PLC-26 as an orange solid (28.0 mg, 26% yield). MS (APCI): Chemical formula: C 58 H 53 BF5N3O 10 Calculated value for ([MH] - )=1057; Measured value: 1057. 1H NMR(400MHz,CDCl2CDCl2)8.67(d,J=8.0Hz,1H), 8.62(d,J=8.0Hz,1H),8.26(d,J=2.4Hz,1H ), 8.07(d,J=8.0Hz,1H), 7.79(bs,4H), 7.77(dd,J=8.0Hz,2.0Hz,1H), 7.51(d,J=8.0Hz,1H) , 7.37(d,J=8.0Hz,1H), 6.73(s,2H), 4.45(t,J=6.0Hz,2H), 4.27(q,J=7.2Hz,4H), 4.09(m,2 H), 3.84(m,4H), 3.74(m,4H), 2.82(s,6H), 2.07(s,6H), 1.72(s,6H), 1.33(t,J=7.2Hz,6H).

[0374] Synthesis of compound PLC-27 [ka]

[0375] Compound PLC-27.1:9-bromo-2-(3-hydroxypropyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione A stirring bar was attached to a 100 mL flask. Compound PLC-3.3 (500.0 mg, 1.4 mmol), 3-aminopropan-1-ol (204.6 mg, 2.7 mmol), and DMAP (11.6 mg, 0.1 mmol) in DMF (15 ml) were degassed at room temperature into the flask. The reaction mixture was heated to 165 °C and the reaction was held at this temperature for 2 hours. TLC and LC-MS indicated completion of the reaction. The reaction was cooled to room temperature. H₂O (85 ml) was added to precipitate the product. The precipitate was collected by filtration. The solid was washed with H₂O (150 ml) and further dried in a vacuum oven at 100 °C for 3 hours to obtain compound PLC-27.1 as a yellow solid for the next step without further purification. 455.0 mg, 79% yield. MS (APCI): Chemical formula: C 21 H 14 Calculated value for BrNO4 ([MH] - )=423; Measured value: 423. 1H NMR(400MHz,CDCl2CDCl2)8.62(d,J=8.0Hz,1H), 8.59(d,J=8.0Hz,1H), 8.18(s,1H), 7.91(d,J=8.0Hz,1H), 7.64(dd,J=8.0H z,J=2.0Hz,1H), 7.33(d,J=8.0Hz,1H), 7.28(d,J=8.0Hz,1H), 4.32(t,J=6.0Hz,2H), 3.56(m,2H), 3.16(bs,1H), 1.98(m,2H).

[0376] Compound PLC-27.2: 2-(3-hydroxypropyl)-9-(perfluorophenyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione A stirring bar was attached to a 100 mL flask. Compound PLC-27.1 (400.0 mg, 0.9 mmol), (perfluorophenyl)boronic acid (240.0 mg, 1.1 mmol), Pd2(dba)3 (43.0 mg, 0.05 mmol), CsF (285.6 mg, 1.9 mmol), Ag2O (259.4 mg, 1.1 mmol), and (t-Bu)3P (1.9 ml, 1.9 mmol) in DMF (30 ml) were degassed at room temperature into the flask. The reaction mixture was heated to 80 °C and the reaction product was held at this temperature overnight. The reaction was monitored using TLC. After completion, the reaction product was purified by silica gel flash chromatography using toluene in hexane (5% → 10% → 50% → 70%) as the eluent to obtain pure compound PLC-27.2 as a yellow solid (136.0 mg, 28% yield). MS(APCI):Chemical formula:C 27 H 14 Calculated value for F5NO4 ([MH]) - )=511; Measured value: 511. 1H NMR(400MHz,CDCl2CDCl2)8.57(d,J=8.0Hz,1H), 8.55(d,J=8.0Hz,1H), 8.07(s,1H), 7.92(d,J=8.0Hz,1H), 7.53(d,J=8.0H z,1H), 7.46(d,J=8.0Hz,1H), 7.32(d,J=8.0Hz,1H), 4.25(t,J=6.0Hz,2H), 3.48(m,2H), 3.07(t,J=6.8Hz,1H), 1.90(m,2H).

[0377] Compound PLC-27.3: 2-(3-bromopropyl)-9-(perfluorophenyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione A stirring bar was attached to a 100 mL flask. Compound PLC-27.2 (136.0 mg, 0.3 mmol), CBr4 (176.3 mg, 0.5 mmol), PPh3 (140.2 mg, 0.5 mmol), and DCE (12 ml) were added to the flask. The solution was degassed at room temperature. The reactants were held at this temperature for 30 minutes. The reaction was monitored using TLC and LC-MS. After completion, the reactants were purified by silica gel flash chromatography using toluene in hexane (5% → 10% → 50% → 70%) as the eluent, and pure compound PLC-27.3 was obtained as a yellow solid (116.0 mg, 76% yield). MS (APCI): Chemical formula: C 27 H 13 Calculated values ​​for BrF5NO3 ([M+H] + )=573; Measured value: 573. 1 H NMR(400MHz,CDCl2CDCl2)8.64(d,J=8.0Hz,1H), 8.61(d,J=8.0Hz,1H), 8.15(d,J=1.6Hz,1H), 7.99(d,J=8.0Hz,1H), 7.61(m, 1H), 7.54(d,J=8.0Hz,1H), 7.39(d,J=8.0Hz,1H), 4.32(t,J=6.8Hz,2H), 3.54(t,J=6.8Hz,2H), 2.34(quintet,J=6.8Hz,2H).

[0378] Compound PLC-27.4: 4-(3-(1,3-dioxo-9-(perfluorophenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propoxy)-2,6-dimethylbenzaldehyde Compound PLC-27.3 (50.0 mg, 0.09 mmol), 4-hydroxy-2,6-dimethylbenzaldehyde (15.7 mg, 0.1 mmol), K2CO3 (24.0 mg, 0.2 mmol), and DMF (2 ml) were added to a 25 ml vial. The mixture was sonicated at room temperature for 2 minutes. Then, it was heated to 75°C and stirred at this temperature for 4 hours. TLC (50% siRNA in hexane) indicated completion of the reaction. The reaction mixture was purified by silica gel flash chromatography using siRNA in DCM (0% → 40%) as the eluent to obtain pure compound PLC-27.4 as a yellow solid (29.0 mg, 48% yield). MS (APCI): Chemical formula: C 36 H 22 Calculated value for F5NO5 ([MH] - )=643; Measured value: 643. 1 H NMR(400MHz,CDCl2CDCl2) δ 10.43(s,1H), 8.63(d,J=8.0Hz,1H), 8.59(d,J=8.0Hz,1H), 8.15(bs,1H), 7.99(d,J=8.0Hz,1H), 7.61(d,J=8.0Hz,1H), 7.54(d,J=8. 0Hz,1H), 7.38(d,J=8.0Hz,1H), 6.55(s,2H), 4.39(t,J=6.8Hz,2H), 4.17(t,J=6.8Hz,2H), 2.56(s,6H), 2.26(quintet,J=6.8Hz,2H).

[0379] Compound PLC-27: Diethyl 10-(4-(3-(1,3-dioxo-9-(perfluorophenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate An air condenser and stirring bar were attached to a 50 mL two-necked round-bottom flask. Compound 27.4 (60.0 mg, 0.1 mmol) and ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (32.7 mg, 0.2 mmol) were added to the flask, followed by anhydrous dichloroethane (5 ml). Ar was sprinkled over the reaction mixture for 30 minutes, and then p-TsOH·H2O (0.7 mg, 0.006 mmol) was added. The reaction solution was heated to 65 °C and held at this temperature overnight. The reaction mixture was then cooled to room temperature and DDQ (11.2 mg, 0.05 mmol) was added. The reaction mixture was held at room temperature for 30 minutes. BF3·OEt2 (0.13 mL, 1.1 mmol) and Et3N (0.10 mL, 0.7 mmol) were then added at room temperature. The reaction mixture was heated to 60 °C and held at this temperature for 1 hour. The reaction mixture was loaded onto silica gel and purified by flash chromatography using ammonium in DCM (0% → 10%) as an eluent to obtain pure compound PLC-27 as an orange solid (77.0 mg, 85% yield). MS(APCI): Chemical formula: C 54 H 43 Calculated values ​​for BF7N3O8 ([MH] - )=1005; Measured value: 1005. 1 H NMR(400MHz,CDCl2CDCl2) 8.64(d,J=8.0Hz,1H), 8.61(d,J=8.0Hz,1H), 8.15(bs,1H), 8.00(d,J=8.0Hz,1H) , 7.61(d,J=8.0Hz,1H), 7.54(d,J=8.0Hz,1H), 7.39(d,J=8.0Hz,1H), 6.67(s,2H) , 4.41(t,J=6.8Hz,2H), 4.27(q,J=7.2Hz,4H), 4.171(t,J=6.8Hz,2H), 2.82(s,6H) ), 2.28(quintet,J=6.8Hz,2H), 2.05(s,6H), 1.72(s,6H), 1.34(t,J=7.2Hz,6H).

[0380] Synthesis of compound PLC-29 [ka]

[0381] Compound PLC-29.1:6-(2-nitro-4-(trifluoromethyl)phenoxy)-1H,3H-benzo[de]isochromene-1,3-dione A 1 L 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter, stopper, and flow control valve were attached to the flask. The system was flushed with argon. 6-bromo-1H,3H-benzo[de]isochromen-1,3-dione (40.0 mmol, 11.084 g) and 2-nitro-4-(trifluoromethyl)phenol (60.0 mmol, 8.44 mL) were added to the flask, followed by anhydrous NMP (150 mL). NaOH (20.0 mmol, 800 mg) and copper (powder) (20.0 mmol, 1271 mg) were added to the flask, followed by anhydrous NMP (25 mL). The heat block was set to 170°C and the flask was stirred under an argon atmosphere. The reaction mixture was stirred at this temperature overnight. The reaction mixture was cooled to room temperature and treated with water (175 mL) and 1N HCl (44 mL). The reaction mixture was further diluted with water (325 mL) to obtain a sticky precipitate. The reaction mixture was decanted from the sticky precipitate and washed with water. The crude product was evaporated to dryness under vacuum, then dissolved in DCM and evaporated onto approximately 65 g of flash silica gel. Purification was performed by silica gel flash chromatography (330 g, solids, equilibrated with 100% hexane, elution 100% (2 CV) → 100% DCM (20 CV)). The fraction containing the product was collected and evaporated to dryness under vacuum. A light brown solid, 1.558 g (10% yield), was obtained (approximately 80% purity). It was used in the next step without further purification. MS (APCI): Chemical formula: C 19 Calculated value for H8F3NO6: (M+H) = 404; Measured value: 404.

[0382] Compound PLC-29.2: (6-(2-amino-4-(trifluoromethyl)phenoxy)-1H,3H-benzo[de]isochromene-1,3-dione) Compound PLC-29.2 was synthesized in the same manner as described above from compound PLC-29.1 (3.47 mmol, 1.400 g), SnCl2·2H2O (13.88 mmol, 3131 mg), and 4N HCl (34.7 mmol, 8.7 mL) in 2 MeTHF (30 mL). After normal workup, the product was of sufficient purity for use in the next step. 877 mg (68% yield) was obtained. MS (APCI): Chemical formula: C 19 H 10 Calculated value for F3NO4 (M+H) = 374; measured value: 374. 1 ¹H NMR (400MHz, tetrachloroethane-d2) δ 8.85 (dd, J=8.4, 1.2Hz, 1H), 8.69 (dd, J=7.3, 1.2Hz, 1H), 8.49 (d, J=8.3Hz, 1H), 7.91 (dd, J=8.4, 7.3Hz, 1H), 7.20 (d, J=2.0Hz, 1H), 7.17~7.07 (m, 2H), 6.98 (d, J=8.3Hz, 1H), 4.07 (s, 2H).

[0383] Compound PLC-29.3: (9-(trifluoromethyl)-1H,3H-isochromeno[6,5,4-mna]xanthene-1,3-dione) Compound PLC-29.3 was synthesized from compound PLC-29.2 (2.344 mmol, 875 mg), NaNO2 (17.58 mmol, 1.213 g), concentrated HCl (11.72 mmol, 12.1 N, 0.969 mL), and CuSO4·5H2O (16.06 mmol, 4.009 g). The crude product was evaporated under vacuum onto approximately 30 g of flash silica gel. Purification was performed by silica gel flash chromatography (220 g, solid content, no equilibration, elution 100% hexane (2 CV) → 100% DCM (20 CV) → isocratic DCM + 0.5% siRNA modifier). The fraction containing the product was evaporated to dryness under vacuum. A yellow solid, 509 mg (61% yield) was obtained. MS (APCI): Chemical formula: C 19 Calculated value for H7F3O4: (M+H) = 357; Measured value: 357. 1¹H NMR (400MHz, tetrachloroethane-d2) δ 8.64 (d, J=7.9Hz, 1H), 8.60 (d, J=8.3Hz, 1H), 8.34~8.28 (m, 1H), 8.04 (d, J=7.9Hz, 1H), 7.82 (dd, J=8.9, 2.0Hz, 1H), 7.52 (d, J=8.6Hz, 1H), 7.40 (d, J=8.3Hz, 1H).

[0384] Compound PLC-29.4: (2-(4-(1,3-dioxo-9-(trifluoromethyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)phenyl)acetic acid) Compound PLC-29.4 was synthesized in the same manner as described above from compound PLC-29.3 (0.702 mmol, 250 mg), 2-(4-aminophenyl)acetic acid (1.754 g, 265 mg), and DMAP (0.0521 mmol, 6.3 mg) in DMF (10 mL). After workup and trituration, the compound was dried in a vacuum oven at approximately 140°C. 366 mg (107% yield) was obtained. MS(APCI): Chemical formula: C 19 Calculated value (M+H) for H7F3O4: 490; Measured value: 490. 1 H NMR(400MHz,DMSO-d6) δ 8.65(d,J=2.2Hz,1H), 8.45~8.37(m,4H), 7.90(dd,J=8.8,2.2Hz,1H), 7.62~7.56(m,1H), 7.45~7.38(m,2H), 7.31~7.24(m,2H), 3.68(s,2H).

[0385] Compound PLC-29: Diethyl 10-(4-(2-(4-(1,3-dioxo-9-(trifluoromethyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)phenyl)acetoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound PLC-29 was synthesized in the same manner as described above from compound PLC-1.1 (0.050 mmol, 25.6 mg), compound PLC-29.4 (0.075 mmol, 37 mg), DMAP·pTsOH salt (0.100 mmol, 29.4 mg), and EDC·HCl (0.150 mmol, 28.8 mg). The crude product was diluted with hexane and loaded onto approximately 30 g of flash silica gel in a solid loader. The product was purified by silica gel flash chromatography (80 g, solid content, no equilibration, elution 100% hexane / 0.5% siRNA modifier (2 CV) → 100% DCM / 0.5% siRNA modifier (10 CV) → 100% DCM / 1% siRNA modifier (20 CV) → 100% DCM / 2% siRNA modifier (20 CV) → 100% DCM / 4% siRNA modifier (20 CV)). The fraction containing the product was evaporated to dryness under vacuum. An orange solid, 46 mg (94% yield) was obtained. MS(APCI): Chemical formula: C 54 H 43 Calculated value (M-) for BF5N3O9: 983; measured value: 983. 1 ¹H NMR (400MHz, tetrachloroethane-d2) δ 8.68 (d, J=7.8Hz, 1H), 8.64 (d, J=8.3Hz, 1H), 8.34 (d, J=2.1Hz, 1H), 8.07 (d, J=8.0Hz, 1H), 7.81 (dd, J=8.9, 2.0Hz, 1H), 7.67~7.62 (m, 2H), 7.52 (d, J=8.6Hz, 1H), 7.41(d,J=8.3Hz,1H), 7.40~7.35(m,2H), 7.05(s,2H), 4.28(q,J=7.1Hz,4 H), 4.01(s,2H), 2.84(s,6H), 2.16(s,6H), 1.73(s,6H), 1.34(t,J=7.1Hz,6H).

[0386] Synthesis of compound PLC-32 [ka]

[0387] Compound PLC-32.1:9-bromo-2-(6-hydroxyhexyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione Compound PLC-32.1 was synthesized from compound PLC-3.3 (6.534 mmol, 2.401 g), 6-aminohexane-1-ol (13.08 mmol, 1533 mg), and DMAP (1.962 mmol, 240 mg) in the same manner as described above. The crude product was filtered, washed with water, and the wet precipitate was used in the next step without further purification. MS(APCI): Chemical formula: C 24 H 20 Calculated value (M+H) for BrNO4: 466; Measured value: 466.

[0388] Compound PLC-32.2 2-(6-hydroxyhexyl)-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione Compound PLC-32.2 was synthesized in the same manner as described above at 80°C from compound PLC-32.1 (assuming 100% yield, 6.534 mmol, 3.047 g), (4-(trifluoromethyl)phenyl)boronic acid (13.068 mmol, 2.482 g), K2CO3 (17.969 mmol, 2483 mg), and Pd(dppf)Cl2 (0.4574 mmol, 335 mg) in THF (120 mL) / DMF (24 mL) / H2O (12 mL). After adding water and filtering, the resulting precipitate was washed with water and then methanol. The product was dried by suction and then by vacuum. 1.191 g (34% yield relative to compound PLC-3.3, 2 steps) was obtained. MS(APCI): Chemical formula: C 31 H 24 Calculated value for F3NO4 (M+H) = 532; measured value: 532.

[0389] Compound PLC-32.3: 2-(6-bromohexyl)-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione A stirring bar was placed in 250 mL of 2N RBF, and a gas adapter / finned condenser and flow controller were attached. Compound PLC-32.2 (2.239 mmol, 1.190 g) was added to the flask, followed by 48% HBr / H2O (30 mL). The heat block was set to 130°C, and the reaction mixture was stirred at this temperature for 3 hours. Another portion of 48% HBr / H2O (30 mL) was added, and the reaction mixture was stirred overnight at 130°C. The reaction mixture was cooled to room temperature, diluted with water (approximately 100 mL), and the precipitate was filtered off and washed with water, then methanol. The product was loaded onto approximately 25 g of silica gel in a loader. The product was purified by silica gel flash chromatography (120 g, solids, equilibrated with 0% Â / DCM, 0% (2 CV) → 10% Â / DCM (20 CV)). The fraction containing the product was collected and evaporated to dryness under vacuum. A substance with a purity of approximately 80% was obtained. A yellow solid, 1.073 g (80% yield), was obtained. MS(APCI): Chemical formula: C 31 H 23 Calculated value (M+H) for BrF3NO3: 594; Measured value: 594. 1 H NMR(400MHz,TCE) δ 8.63(d,J=7.9Hz,1H), 8.58(d,J=8.3Hz,1H), 8.23(d,J=2.1Hz,1H), 8.03(d,J=8.0Hz,1H), 7.84~7.73(m,5H), 7.49(d,J=8.6Hz,1H), 7 .34(d,J=8.3Hz,1H), 4.19~4.09(m,2H), 3.44(td,J=6.8,1.9Hz,2H), 1.90(p,J=6.9Hz,2H), 1.75(p,J=7.8Hz,2H), 1.57~1.38(m,4H).

[0390] Compound PLC-32.4 4-((6-(1,3-dioxo-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)hexyl)oxy)-2,6-dimethylbenzaldehyde Compound PLC-32.4 was synthesized in dry DMF (10 mL) from compound PCL-32.3 (0.200 mmol, 119 mg), 4-hydroxy-2,6-dimethylbenzaldehyde (0.300 mmol, 45 mg), and K2CO3 (0.260 mmol, 36 mg). The reaction mixture was sonicated for 15 minutes, then stirred in a 65°C heat block for 7 hours. Heating was stopped, and water was added to the warm reaction mixture (approximately 100 mL), which did not produce a precipitate. The aqueous layer was saturated with NaCl and then extracted with THF (1 × 200 mL, 2 × 50 mL). The combined organic layers were dried over MgSO4, filtered, and evaporated to dryness under vacuum. The crude product was dissolved in DCM and loaded onto approximately 5 g of silica gel in a loader. The product was purified by silica gel flash chromatography (80 g, solids content, equilibration 70% DCM / hexane, elution 70% (2 CV) → 100% DCM / hexane (5 CV) → isocratic 100% DCM / hexane (5 CV) → 0% siRNA / DCM (0 CV) → isocratic 0% siRNA / DCM (5 CV) → 10% siRNA / DCM (20 CV)). The fraction containing the product was evaporated to dryness under vacuum. A yellow solid, 95 mg (71% yield) was obtained. MS (APCI): Chemical formula: C 40 H 32 Calculated value for F3NO5 (M+H) = 664; measured value: 664. 1 H NMR(400MHz,TCE) δ 10.42(s,1H), 8.64(d,J=7.9Hz,1H), 8.59(d,J=8.3Hz,1H), 8.25(d,J=2.2Hz,1H), 8.05(d,J=8.0Hz,1H), 7.84~7.74(m,5H), 7.51(d,J=8. 5Hz,1H), 7.36(d,J=8.3Hz,1H), 6.60(s,2H), 4.20~4.15(m,2H), 4.01(t,J=6.4Hz,2H), 2.59(s,6H), 1.89~1.70(m,4H), 1.60~1.43(m,4H).

[0391] Compound PLC-32: Diethyl 10-(4-((6-(1,3-dioxo-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)hexyl)oxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound PLC-32 was synthesized in the same manner as compound 32, from compound PLC-32.4 (0.1401 mmol, 93 mg), ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (0.0.2943 mmol, 49 mg) in dried DCE (20 mL), followed by pTsOH·H2O (0.0140 mmol, 2.7 mg), then DDQ (0.0.2382 mmol, 54 mg), 2×Et3N (1.121 mmol, 0.156 mL), and BF3·OEt2 (1.682 mmol, 0.208 mL). The crude reaction mixture was diluted with hexane (approximately 25%) and then loaded onto approximately 5 g of silica gel in a loader. The product was purified by silica gel flash chromatography (80 g, solids content, equilibration 70% DCM / hexane, elution 70% (2 CV) → 100% DCM / hexane (5 CV) → isocratic 100% DCM / hexane (5 CV) → 0% siRNA / DCM (0 CV) → isocratic 0% siRNA / DCM (5 CV) → 10% siRNA / DCM (20 CV)). The fraction containing the product was evaporated to dryness under vacuum. An orange solid, 26 mg (18% yield) was obtained. MS (APCI): Chemical formula: C 58 H 53 Calculated value (M+H) for BF5N3O8: 1026; Measured value: 1026. 1H NMR(400MHz,TCE) δ 8.56(d,J=7.8Hz,1H), 8.51(d,J=8.4Hz,1H), 8.16(d,J=2.3Hz,1H), 7.97(d,J=8.0Hz ,1H), 7.77~7.65(m,5H), 7.42(d,J=8.6Hz,1H), 7.27(d,J=8.3Hz,1H), 6.66(s,2H), 4. 18(q,J=7.1Hz,4H), 4.10(dd,J=8.8,6.6Hz,2H), 3.92(t,J=6.5Hz,2H), 2.74(s,6H), 1 .99(s,6H), 1.82~1.67(m,4H), 1.65(s,6H), 1.52~1.38(m,4H), 1.24(t,J=7.1Hz,6H).

[0392] Synthesis of compound PLC-33 [ka]

[0393] Compound PLC-33.1: 2-(2-(2-methoxyethoxy)ethoxy)ethyl 2,4-dimethyl-1H-pyrrole-3-carbonxylate) A stirring bar was placed in 100 mL of 2N RBF, and a gas adapter / finned condenser and flow controller were attached. The system was flushed with argon. NaH (60% mineral oil, 45.00 mmol, 1800 mg) was added to the flask. The mixture was stirred at room temperature, and 2-(2-(2-methoxyethoxy)ethoxy)ethane-1-ol (90.00 mmol, 14.4 mL) was carefully added. When the generation of hydrogen gas stopped, ethyl 2,4-dimethyl-1H-pyrrole-3-carbonxylate (30.00 mmol, 5.016 g) was added. The system was closed and stirred under an argon atmosphere. The heat block was set to 130°C, and the reaction mixture was stirred at this temperature for 30 minutes. LCMS showed a product:starting material ratio of approximately 45:55. The reaction was continued at 130°C for several more hours, but the ratio hardly changed. A vent was installed at the top of the findenser and opened to allow ethanol to escape. After heating for approximately 5 hours, less than 5% of the starting ester remained. The reaction mixture was cooled to room temperature and water was added. Since no precipitate formed, the reaction mixture was treated with NaCl to break up the emulsion, and then extracted with ethyl acetate (3 × 100 mL). The combined organic layer was washed with brine (50 mL), dried over MgSO4, filtered, and evaporated to dryness under vacuum. A dark brown oily substance was obtained. The vial was heated at 140°C under an argon stream to remove excess alcohol. 6.839 g (80% yield) was obtained. MS(APCI): Chemical formula: C 14 H 23 Calculated value for NO5 (M+H) = 286; measured value: 286. 1 H NMR(400MHz,TCE) δ 8.07(s,1H), 6.39(dd,J=2.3,1.2Hz,1H), 4.38~4.31(m,2H), 3.81~3.74(m,2H), 3.69~3.65(m ,2H), 3.65~3.58(m,4H), 3.56~3.50(m,2H), 3.35(s,3H), 2.48(s,3H), 2.23(d,J=1.1Hz,3H).

[0394] Compound PLC-33.2: Bis(2-(2-(2-methoxyethoxy)ethoxy)ethyl)5,5-difluoro-10-(4-hydroxy-2,6-dimethylphenyl)-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound PLC-33.2 was synthesized in the same manner as described above, from compound PLC-33.1 (3.588 mmol, 1024 mg), 4-hydroxy-2,6-dimethylbenzaldehyde (1.750 mmol, 263 mg), and pTsOH·H2O (0.175 mmol, 33 mg) in dry DCE (50 mL), followed by DDQ (2.975 mmol, 675 mg), 2×Et3N (14.00 mmol, 1.95 mL), and BF3·OEt2 (14.00 mmol, 2.59 mL), at room temperature and then at 50°C. The crude reaction mixture was loaded onto approximately 30 g of silica gel in a loader. The mixture was purified by silica gel flash chromatography (120 g, equilibrated 30% siRNA / DCM, eluted 30% (2 CV), → 100% siRNA (20 CV)). Elution was obtained as a broad peak. The fraction containing the product was evaporated to dryness under vacuum. A thick, rubbery product, 1.055 g (80% yield), was obtained. MS(APCI): Chemical formula: C 37 H 51 BF2N2O 11 The calculated value for this is (M+H) = 749; the measured value is 749. 1 H NMR(400MHz,TCE) δ 6.61(s,2H), 4.28(t,J=4.8Hz,4H), 3.67(t,J=4.8Hz,4H), 3.59~3.48(m,12 H), 3.47~3.38(m,4H), 3.27(s,7H), 2.75(s,6H), 1.97(s,6H), 1.66(s,6H).

[0395] Compound PLC-33: Bis(2-(2-(2-methoxyethoxy)ethoxy)ethyl)10-(4-(2-(4-(1,3-dioxo-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)phenyl)acetoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound PLC-33.2 (0.045 mmol, 34 mg), compound PLC-3.5 (0.07875 mmol, 45 mg), DMAP·pTsOH salt (0.090 mmol, 27 mg), and EDC·HCl (0.180 mmol, 35 mg) were combined in a 40 mL screw-cap vial using a stirring bar. Dry DCM (10 mL) was added to the vial, and the reaction mixture was stirred at room temperature for 90 minutes. The crude reaction mixture was loaded onto approximately 20 g of silica gel in a loader. Purification was performed by silica gel flash chromatography (80 g, solids content, equilibration 10% Â / DCM, elution 50% (2 CV) → 100% EtOAC (20 CV)). An orange solid, 36 mg (62% yield), was obtained. MS (APCI): Chemical formula: C 70 H 67 BF5N3O 15 The calculated value for (M+H) is 1296; the measured value is 1296. 1 H NMR(400MHz,TCE) δ 8.69(d,J=7.8Hz,1H), 8.64(d,J=8.3Hz,1H), 8.29(d,J=2.2Hz,1H), 8.11(d,J=8.1Hz,1H) , 7.85~7.76(m,5H), 7.66~7.61(m,2H), 7.55(d,J=8.6Hz,1H), 7.41(d,J=8.3Hz,2H), 7.40 ~7.34(m,2H), 7.06(s,2H), 4.38(dd,J=5.9,3.7Hz,4H), 4.01(s,2H), 3.79~3.72(m,4H), 3 .68~3.55(m,12H), 3.55~3.48(m,4H), 3.35(s,6H), 2.85(s,6H), 2.16(s,6H), 1.74(s,6H).

[0396] Synthesis of compound PLC-34 [ka]

[0397] Compound PLC-34: Bis(2-(2-(2-methoxyethoxy)ethoxy)ethyl)5,5-difluoro-10-(4-(2-(4-(9-(4-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)phenyl)acetoxy)-2,6-dimethylphenyl)-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound PLC-33.2 (0.045 mmol, 34 mg), compound PLC-17.6 (0.0675 mmol, 45 mg), DMAP·pTsOH salt (0.090 mmol, 27 mg), and EDC·HCl (0.1350 mmol, 30 mg) were combined in a 40 mL screw-cap vial using a stirring bar, and the synthesis was carried out in the same manner as described above. The crude product was loaded onto approximately 20 g of silica gel in a loader. Purification was performed by flash chromatography (80 g, solids content, equilibration 30% Â / DCM, elution 30% (2 CV) → 100% Â (20 CV) → isocratic 100% Â (until the product was completely eluted)). Elution was observed as a broad peak. The fraction containing the product was evaporated to dryness under vacuum. An orange solid, 34 mg (54% yield) was obtained. MS (APCI): Chemical formula: C 76 H 82 BF2N3O 19 The calculated value for (M+H) is 1391; the measured value is 1391. 1H NMR(400MHz,TCE) δ 8.68(d,J=7.9Hz,1H), 8.63(d,J=8.3Hz,1H), 8.25(d,J=2.1Hz,1H), 8.11(d,J=8.2Hz,1H), 7.78(dd,J=8.7,2. 1Hz,1H), 7.64(dd,J=8.6,2.3Hz,4H), 7.50(d,J=8.6Hz,1H), 7.44~7.34(m,3H), 7.09(d,J=8.7Hz,2H), 7.06(s ,2H), 4.38(t,J=4.9Hz,4H), 4.22(t,J=4.8Hz,2H), 4.01(s,2H), 3.90(t,J=4.8Hz,2H), 3.76(dt,J=5.5,2.7Hz ,6H), 3.71~3.54(m,18H), 3.54~3.49(m,4H), 3.38(s,3H), 3.35(s,6H), 2.85(s,6H), 2.16(s,6H), 1.74(s,6H).

[0398] Synthesis of compound PLC-35

change

[0399] Compound PLC-35.1: 2,2,2-Torotron 2,4-Toro-1H-Toro-3-Torotron Compound PLC-35.1 was synthesized at 130°C from ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (12.00 mmol, 2.006 g), NaH (60% mineral oil, 36.00 mmol, 1440 mg), and 2,2,2-trifluoroethane-1-ol (120.0 mmol, 8.74 mL) in the same manner as described above. Due to the low boiling point of the target alcohol, all solvent was evacuated and 2,2,2-trifluoroethane-1-ol (8.74 mL) was added again. The conversion could only be carried out to about 20%. The crude material was loaded onto approximately 20 g of silica gel in a loader. It was purified by silica gel flash chromatography (120 g, solids, equilibration 10% siRNA / hexane, elution 10% (2 CV) → 50% siRNA / hexane (20 CV)). The fraction containing the product was evaporated to dryness under vacuum. 468 mg (18% yield) was obtained. MS (APCI): Chemical formula: C9H 10 Calculated value for F3NO2: (M+H) = 222; Measured value: 222. 1 H NMR (400MHz,TCE) δ 8.12(s,1H), 6.42(dd,J=2.3,1.2Hz,1H), 4.61(q,J=8.6Hz,2H), 2.49(s,3H), 2.24(d,J=1.1Hz,3H).

[0400] Compound PLC-35.2: Bis(2,2,2-trifluoroethyl)5,5-difluoro-10-(4-hydroxy-2,6-dimethylphenyl)-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound PLC-35.2 was synthesized in the same manner as described above from compound PLC-35.1 (1.575 mmol, 348 mg), 4-hydroxy-2,6-dimethylbenzaldehyde (0.750 mmol, 113 mg), and pTsOH·H2O (0.300 mmol, 57 mg), then DDQ (1.275 mmol, 289 mg), and 2×Et3N (6.00 mmol, 0.84 mL) and BF3·OEt2 (9.00 mmol, 1.10 mL) in dried DCE (20 mL), at 60°C and then at 50°C. The crude reaction mixture was diluted 1:1 with hexane and then loaded onto approximately 30 g of silica gel in a loader. The mixture was purified by silica gel flash chromatography (220 g, solids, equilibration 5% siRNA / hexane, elution 5% (2 CV) → 30% siRNA / hexane (10 CV)). The fraction containing the product was evaporated to dryness. An orange solid, 208 mg (45% yield), was obtained. MS(APCI): Chemical formula: C 27 H 25 Calculated value (M+H) for BF8N2O5: 621; Measured value: 621. 1 H NMR (400MHz, TCE) δ 6.72(s,2H), 4.63(q,J=8.5Hz,4H), 2.85(s,6H), 2.07(s,6H), 1.77(s,6H).

[0401] Compound PLC-38: Bis(2,2,2-trifluoroethyl)10-(4-(2-(4-(1,3-dioxo-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-phenyl)acetoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound 35.2 (0.060 mmol, 37 mg), Compound 3.5 (0.105 mmol, 59 mg), DMAP·pTsOH salt (0.120 mmol, 35 mg), and EDC·HCl (0.240 mmol, 46 mg) were combined with 10 mL of dry DCM in a 40 mL screw-cap vial using a stirring bar, and synthesized in the same manner as for Compound 36. The solvent was evaporated, and the crude reaction mixture was incorporated into toluene and loaded onto approximately 20 g of silica gel in a loader. Purification was performed by silica gel flash chromatography (80 g, solids content, equilibration 0% Â / toluene, elution 0% (2 CV) → 0% Â / toluene with 0.5% Â modifier). The product eluted rapidly. An orange solid, 21 mg (30% yield) was obtained. MS (APCI): Chemical formula: C 60 H 41 BF 11 Calculated value for N3O9 (M+H) = 1168; measured value: 1168. 1 H NMR(400MHz,TCE) δ 8.69(d,J=7.9Hz,1H), 8.64(d,J=8.3Hz,1H), 8.29(d,J=2.2Hz,1H), 8.11(d,J=8.1Hz,1H), 7.85~7.76(m,5H), 7.68~7.61(m,2H), 7.55(d,J=8.7Hz,1H), 7.40(s,0H), 7.40~7.35(m,2H), 4.63(q,J=8.5Hz,4H), 4.02(s,2H), 2.86(s,6H), 2.16(s,6H), 1.76(s,6H).

[0402] Synthesis of compound PLC-36 [ka]

[0403] Compound PLC-36.1:tert-butyl4-(2-(3-hydroxypropyl)-1,3-dioxo-2,3-dihydro-1H-xantheno[2,1,9-def]isoquinoline-9-yl)benzoate Compound PLC-36.1 was synthesized at 80°C from compound 27.1 (1.30 mmol, 552 mg), (4-(tert-butoxycarbonyl)phenyl)boronic acid (2.60 mmol, 577 mg), K2CO3 (3.575 mmol, 494 mg), and Pd(dppf)Cl2 (0.0910 mmol, 67 mg) in THF (30 mL) / DMF (6 mL) / water (3 mL), similar to compound 32.2. After adding water, the product was filtered, washed with water, and then washed with methanol. The compound was dried by suction and then by vacuum. A yellowish-brown solid, 633 mg (93% yield), was obtained. MS(APCI): Chemical formula: C 32 H 27 Calculated value for NO6 (M+H) = 522; measured value: 522. 1 H NMR(400MHz,TCE) δ 8.66(d,J=7.9Hz,1H), 8.61(d,J=8.3Hz,1H), 8.27(d,J=2.2Hz,1H), 8.13(d,J =8.0Hz,2H), 8.06(d,J=7.9Hz,1H), 7.80(dd,J=8.6,2.1Hz,1H), 7.74(d,J=8. 0Hz,2H), 7.51(d,J=8.6Hz,1H), 7.37(d,J=8.3Hz,1H), 4.33(t,J=6.0Hz,2H), 3.57(q,J=6.0Hz,2H), 3.20(t,J=6.9Hz,1H), 2.07~1.91(m,2H), 1.64(s,9H).

[0404] Compound 36.2: tert-butyl 4-(2-(3-bromopropyl)-1,3-dioxo-2,3-dihydro-1H-xantheno[2,1,9-def]isoquinoline-9-yl)benzoate A 100 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter and a flow control valve were attached to the flask. The system was flushed with argon. Compound PLC-36.1 (1.208 mmol, 630 mg) and dried DCM (30 mL) were added to the flask. Under argon, at room temperature, Et3N (2.416 mmol, 0.337 mL) was added, followed by PBr3 (0.046 mL). The reaction mixture was stirred at room temperature for 15 minutes. PBr3 (2.416 mmol, 0.230 mL) was added to the flask and stirring was continued at room temperature for 2 hours. The crude reaction mixture was separated into DCM (50 mL) and water (25 mL). 10 mL of brine was added to break up the emulsion and separate the layers. The reaction mixture was acidified with AcOH and then extracted with DCM (3 × 50 mL). The combined organic layers were dried over MgSO4, filtered, and evaporated to dryness under vacuum. The crude product was dissolved in DCM and loaded onto approximately 20 g of silica gel in a loader. Purification was performed by silica gel flash chromatography (80 g, solids, equilibration 0% siRNA / DCM, elution 0% (2 CV) → 10% siRNA / DCM (20 CV)). The fraction containing the product was evaporated to dryness under vacuum. A yellow solid, 192 mg, and a yield of 27% were obtained. The majority of the starting materials became an unknown byproduct. MS(APCI): Chemical formula: C 32 H 26 Calculated value (M+H) for BrNO5: 584; Measured value: 584. 1 H NMR(400MHz,TCE) δ 8.64(d,J=7.9Hz,1H), 8.59(d,J=8.3Hz,1H), 8.27(d,J=2.2Hz,1H), 8.17~8.09(m,2H), 8.05(d,J=8.0Hz,1H), 7.80(dd,J=8.6,2.1Hz,1H), 7.7 7~7.69(m,2H), 7.50(d,J=8.6Hz,1H), 7.36(d,J=8.3Hz,1H), 4.31(t,J=7.1Hz,2H), 3.54(t,J=6.8Hz,2H), 2.34(p,J=6.9Hz,2H), 1.64(s,9H).

[0405] Compound PLC-36.3 tert-butyl4-(2-(3-(4-formyl-3,5-dimethylphenoxy)propyl)-1,3-dioxo-2,3-dihydro-1H-xantheno[2,1,9-def]isoquinoline-9-yl)benzoate Compound PLC-36.3 was synthesized in the same manner as for compound 34.4 from compound PLC-36.2 (0.1540 mmol, 90 mg), 4-hydroxy-2,6-dimethylbenzaldehyde (0.308 mmol, 46 mg), and K2CO3 in dry DMF (10 mL). The crude reaction mixture was diluted with crushed ice (approximately 100 g). After all components had dissolved, the crude product was filtered off and washed with water. The product was dried by suction, then dissolved in DCM, and evaporated to dryness under vacuum. A yellow solid in quantitative yield was obtained. MS(APCI): Chemical formula: C 41 H 35 Calculated value for NO7 (M+H) = 654; measured value: 654. 1 1H NMR (400MHz, TCE) δ 10.43(s,1H), 8.65(d,J=7.9Hz,1H), 8.59(d,J=8.3Hz,1H), 8.28(d,J=2.1H) z,1H), 8.16~8.10(m,2H), 8.07(d,J=8.0Hz,1H), 7.80(dd,J=8.6,2.1Hz,1H ), 7.78~7.70(m,2H), 7.37(d,J=8.4Hz,1H), 6.55(s,2H), 4.39(t,J=7.0Hz, 2H), 4.18(t,J=6.0Hz,2H), 2.56(s,6H), 2.26(p,J=6.5Hz,2H), 1.64(s,9H).

[0406] Compound PLC-36: Diethyl 10-(4-(3-(9-(4-(tert-butoxycarbonyl)phenyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound PLC-36 was synthesized in the same manner as described above from compound PLC-36.3 (0.154 mmol, 100 mg), ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (0.308 mmol, 52 mg) in dried DCE (20 mL), followed by room temperature TFA (0.020 mL), then DDQ (0.262 mmol, 59 mg), 2×Et3N (1.232 mmol, 0.17 mL), and BF3·OEt2 (1.848 mmol, 0.23 mL). The crude reaction mixture was diluted with hexane and loaded onto approximately 20 g of silica gel in a loader. Purification was performed by silica gel flash chromatography (120 g, solids, equilibration 0% siRNA / toluene, elution 0% (2 CV) → 1% siRNA / toluene (30 CV)). Only partial separation was performed. The fraction containing the pure product was evaporated to dryness under vacuum. 56 mg of pure product (36% yield) was obtained. MS (APCI): Chemical formula: C 59 H 56 BF2N3O 10 The calculated value for (M+H) is 10¹⁶; the measured value is 10¹⁶. 1 H NMR(400MHz,TCE) δ 8.66(d,J=7.9Hz,1H), 8.60(d,J=8.3Hz,1H), 8.29(d,J=2.1Hz,1H), 8.16~8.10(m,2H), 8.08(d, J=8.0Hz,1H), 7.80(dd,J=8.6,2.1Hz,1H), 7.75(d,J=8.3Hz,2H), 7.51(d,J=8.6Hz,1H), 7.38(d, J=8.3Hz,1H), 6.67(s,2H), 4.42(t,J=7.1Hz,2H), 4.27(q,J=7.1Hz,4H), 4.17(t,J=6.1Hz,2H), 2 .82(s,6H), 2.28(p,J=6.3Hz,2H), 2.04(s,6H), 1.72(s,6H), 1.64(s,9H), 1.34(t,J=7.1Hz,6H).

[0407] Synthesis of compound PLC-37 [ka]

[0408] Compound PLC-37.1: 2-ethylhexyl-2,4-dimethyl-1H-pyrrole-3-carboxylate A stirring bar was placed in 100 mL of 2N RBF, and a gas adapter / finned condenser and flow controller were attached. The system was flushed with argon. NaH (60% mineral oil, 36.00 mmol, 1440 mg) was added to the flask. The mixture was stirred at room temperature, and 2-ethylhexane-1-ol (120.00 mmol, 18.8 mL) was carefully added. When the generation of hydrogen gas stopped, ethyl 2,4-dimethyl-1H-pyrrole-3-carbonxylate (12.00 mmol, 2.006 g) was added. The system was closed and stirred under an argon atmosphere. The heat block was set to 130°C, and the reaction mixture was stirred at this temperature with the vent open for 30 minutes. The vent was closed, and the system was heated at 130°C for 2 hours, then the vent was opened again for about 30 minutes. The system was heated again for about 2 hours, and no residual ethyl ester was found by LC-MS. The reaction mixture was cooled to room temperature, quenched with saturated NH4Cl solution, and then diluted with water (approximately 100 mL). The mixture was extracted with DCM (1 × 100 mL, 2 × 50 mL). The combined organic layer was dried over MgSO4, filtered, and evaporated to dryness under vacuum. A dark brown oily substance was obtained. The vial was heated at 140°C under argon flow to remove excess alcohol. A brown oily substance, 2.920 g (97% yield), was obtained. MS(APCI): Chemical formula: C 15 H 25 Calculated value for NO2 (M+H) = 252; measured value: 252. 1 H NMR(400MHz,TCE) δ 4.20~4.05(m,2H), 3.53(d,J=4.9Hz,2H), 2.49(s,3H), 2.24(d,J=1.0Hz,3H), 1.75~1.56(m,4H), 1.52~1.16(m,17H), 1.00~0.79(m,13H).

[0409] Compound PLC-37.2: Bis(2-ethylhexyl)5,5-difluoro-10-(4-hydroxy-2,6-dimethylphenyl)-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound PLC-37.2 was synthesized in the same manner as for compound 32, from compound PLC-37.1 (4.20 mmol, 1056 mg), 4-hydroxy-2,6-dimethylbenzaldehyde (2.00 mmol, 300 mg), and TFA (0.200 mL), then DDQ (3.40 mmol, 772 mg), and 2×Et3N (16.00 mmol, 2.20 mL), and BF3·OEt2 (24.00 mmol, 3.0 mL) in dried DCE (20 mL), at room temperature and then 50 °C. The crude reaction mixture was loaded onto approximately 65 g of silica gel in a loader. The mixture was purified by silica gel flash chromatography (220 g, equilibrated 0% siRNA / hexane, eluted 0% (2 CV), → 20% siRNA / hexane (30 CV)). The fraction containing the product was evaporated to dryness under vacuum. A thick, rubbery product was obtained in an amount of 614 mg (45% yield). MS (APCI): Chemical formula: C 39 H 55 Calculated value (M+H) for BF2N2O5: 681; Measured value: 681. 1 H NMR (400MHz,TCE) δ 6.71(s,2H), 4.24~4.07(m,4H), 2.84(s,6H), 2.07(s,6H), 1.75(s,6H), 1.48~1.22(m,16H), 0.96~0.82(m,10H).

[0410] Compound PLC-37: Bis(2-ethylhexyl)10-(4-(2-(4-(1,3-dioxo-9-(4-(trifluoromethyl)phenyl)-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)phenyl)acetoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-carboxylate Compound PLC-37.2 (0.075 mmol, 51 mg), compound PLC-3.5 (0.113 mmol, 64 mg), DMAP·pTsOH salt (0.150 mmol, 44 mg), and EDC·HCl (0.300 mmol, 58 mg) were combined in a 40 mL screw-cap vial using a stirring bar. Dry DCM (10 mL) was added to the vial, and the reaction mixture was stirred at room temperature for 90 minutes. The crude reaction mixture was loaded onto approximately 20 g of silica gel in a loader. Purification was performed by silica gel flash chromatography (220 g, solids, equilibration 10% Â / hexane, elution 10% (2 CV) → 50% EtOAC / hexane (20 CV)). An orange solid, 69 mg (75% yield), was obtained. MS (APCI): Chemical formula: C 72 H 71 Calculated value (M+H) for BF5N3O9: 1229; Measured value: 1229. 1 H NMR(400MHz,TCE) δ 8.69(d,J=7.9Hz,1H), 8.64(d,J=8.3Hz,1H), 8.29(d,J=2.2Hz,1H), 8.11(d,J=8.1H) z,1H), 7.85~7.77(m,5H), 7.67~7.62(m,2H), 7.55(d,J=8.6Hz,1H), 7.42(d,J=8.3Hz) ,1H), 7.40~7.35(m,2H), 7.07(s,2H), 4.23~4.08(m,4H), 4.02(s,2H), 2.85(s,6H), 2 .16(s,6H), 1.74(s,6H), 1.69~1.56(m,2H), 1.48~1.22(m,16H), 0.95~0.80(m,12H).

[0411] Synthesis of compound PLC-38 [ka]

[0412] Compound PLC-38.1:9-(4-butylphenyl)-2-(3-hydroxypropyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione Compound PLC-38.1 was synthesized at 80°C using the same method as for compound 32.2, from compound PLC-27.1 (1,500 mmol, 636 mg), (4-butylphenyl)boronic acid (3.00 mmol, 534 mg), K2CO3 (4.125 mmol, 570 mg), and Pd(dppf)Cl2 (0.105 mmol, 77 mg) in THF (30 mL) / DMF (6 mL) / water (3 mL). The precipitated compound was filtered, washed with water, and dried under vacuum. A yellowish-brown solid, 655 mg (92% yield), was obtained. MS(APCI): Chemical formula: C 31 H 27 Calculated value for NO4 (M+H) = 478; measured value: 478. 1 H NMR(400MHz,TCE) δ 8.66(d,J=7.9Hz,1H), 8.61(d,J=8.4Hz,1H), 8.26(d,J=2.1Hz,1H), 8.06(d,J=8.0Hz,1H) , 7.79(dd,J=8.6,2.1Hz,1H), 7.61(d,J=7.9Hz,2H), 7.48(d,J=8.6Hz,1H), 7.41~7.30(m, 3H), 4.34(t,J=6.1Hz,2H), 3.57(q,J=6.0Hz,2H), 3.24(t,J=6.9Hz,1H), 2.70(t,J=7.7Hz ,2H), 2.06~1.92(m,2H), 1.75~1.64(m,2H), 1.42(h,,J=7.4Hz,2H), 0.98(t,J=7.3Hz,3H).

[0413] Compound PLC-38.2:3-(9-(4-butylphenyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propyl 4-methylbenzenesulfonate A 100 mL 2N round-bottom flask was placed in an aluminum heat block and a stirring bar was inserted. A finned condenser / gas adapter and a flow control valve were attached to the flask. The system was flushed with argon. Compound PLC-38.1 (0.325 mmol, 155 mg), 4-methylbenzenesulfonic anhydride (1.30 mmol, 424 mg), and dried DCE (20 mL) were added to the flask. The reaction mixture was stirred under argon at room temperature and Et3N (1.463 mmol, 0.20 mL) was added. The reaction mixture was stirred under argon, the heat block was set to 90°C, and the mixture was stirred at this temperature for 1 hour. The reaction mixture was cooled to room temperature and loaded onto approximately 15 g of silica gel in a loader. The mixture was purified by silica gel flash chromatography (80 g, solids, equilibrated 0% HCl / DCM, eluted 0% (2 CV) → 10% HCl / DCM (10 CV)). The fraction containing the product was evaporated to dryness under vacuum. A yellow solid, 157 mg (77% yield), was obtained. MS(APCI): Chemical formula: C 38 H 33 Calculated value for NO6S (M+H) = 632; measured value: 632. 1 H NMR(400MHz,TCE) δ 8.61(d,J=7.9Hz,1H), 8.56(d,J=8.4Hz,1H), 8.24(d,J=2.2Hz,1H), 8.04(d,J=8 .1Hz,1H), 7.81~7.72(m,3H), 7.61(d,J=8.1Hz,2H), 7.47(d,J=8.6Hz,1H), 7.40~ 7.27(m,5H), 4.19(dt,J=11.9,6.6Hz,4H), 2.70(t,J=7.8Hz,2H), 2.42(s,3H), 2. 19~2.07(m,2H), 1.76~1.64(m,2H), 1.42(h,J=7.3Hz,2H), 0.98(t,J=7.4Hz,3H).

[0414] Compound PLC-38.3: 4-(3-(9-(4-butylphenyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propoxy)-2,6-dimethylbenzaldehyde Compound 46.3 was synthesized from compound PLC-38.2 (0.119 mmol, 75 mg), 4-hydroxy-2,6-dimethylbenzaldehyde (0.356 mmol, 53 mg), and K2CO3 (0.332 mmol, 46 mg) in dry DMF (10 mL). The reaction mixture was sonicated for 15 minutes, then stirred in a 65°C heat block for 7 hours. Heating was stopped, and approximately 25 g of crushed ice was added to the reaction mixture. Water (approximately 90 mL) was added, the product was filtered, and washed with water. The product was dried by suction, then dried under vacuum. A yellow solid, 72 mg (100% yield), was obtained. MS(APCI): Chemical formula: C 40 H 35 Calculated value for NO5 (M+H) = 610; measured value: 610. 1 H NMR(400MHz,TCE) δ 10.43(s,1H), 8.63(d,J=7.9Hz,1H), 8.58(d,J=8.3Hz,1H), 8.25(d,J=2.1Hz,1H), 8.05(d,J=8. 0Hz,1H), 7.78(dd,J=8.6,2.1Hz,1H), 7.61(d,J=7.9Hz,2H), 7.47(d,J=8.6Hz,1H), 7.39~7.29( m,3H), 6.55(s,2H), 4.38(t,J=7.1Hz,2H), 4.17(t,J=6.0Hz,2H), 2.70(t,J=7.8Hz,2H), 2.56(s ,6H), 2.26(p,J=6.7Hz,2H), 1.67(p,J=7.6Hz,2H), 1.42(h,J=7.4Hz,2H), 0.98(t,J=7.3Hz,3H).

[0415] Compound PLC-38: Diethyl 10-(4-(3-(9-(4-butylphenyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound PLC-38 was synthesized in the same manner as for compound 32 from compound PCL-38.3 (0.118 mmol, 72 mg), ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (0.307 mmol, 51 mg) in dried DCE (20 mL), followed by TFA (1% vol / vol), then DDQ (0.201 mmol, 46 mg), 2×Et3N (0.944 mmol, 0.130 mL), and BF3·OEt2 (1.420 mmol, 0.175 mL) at 80°C, then at 50°C. The crude reaction mixture was loaded onto approximately 20 g of silica gel in a loader. The mixture was purified by silica gel flash chromatography (80 g, solids, equilibration 0% siRNA / hexane, elution 0% (2 CV) → 50% siRNA / hexane (30 CV)). The fraction containing the product was evaporated to dryness under vacuum. An orange solid, 21 mg (18% yield), was obtained. MS(APCI): Chemical formula: C 58 H 56 Calculated value (M+H) for BF2N3O8: 972; Measured value: 972. 1 H NMR(400MHz,TCE) δ 8.65(d,J=7.9Hz,1H), 8.59(d,J=8.4Hz,1H), 8.26(d,J=2.1Hz,1H), 8.07(d,J=8.1Hz,1H), 7.78(dd,J=8.6,2. 1Hz,1H), 7.65~7.57(m,2H), 7.48(d,J=8.6Hz,1H), 7.37(d,J=8.6Hz,1H), 7.34(d,J=8.2Hz,2H), 6.67(s,2H), 4 .42(t,J=7.1Hz,2H), 4.27(q,J=7.1Hz,4H), 4.17(t,J=6.2Hz,2H), 2.82(s,6H), 2.70(t,J=7.7Hz,2H), 2.34~2. 23(m,2H), 2.04(s,6H), 1.77~1.62(m,8H), 1.42(h,J=7.4Hz,2H), 1.34(t,J=7.1Hz,6H), 0.98(t,J=7.3Hz,3H).

[0416] Synthesis of compound PLC-39 [ka]

[0417] Compound PLC-39.2: 4-(3-(9-(tert-butyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propoxy)-2,6-dimethylbenzaldehyde Compound PLC-39.2 was synthesized from compound 39.1 (0.601 mmol, 279 mg), 4-hydroxy-2,6-dimethylbenzaldehyde (1.802 mmol, 270 mg), and K2CO3 (1.682 mmol, 232 mg) in dry DMF (15 mL). The reaction mixture was sonicated for 15 minutes, then stirred in a 65°C heat block for 7 hours. The crude reaction mixture was diluted with approximately 100 mL of water, and the product was filtered off. The crude precipitate was dissolved in DCM and evaporated to dryness under vacuum. The product was dissolved in DCM and loaded onto approximately 20 g of silica gel in a loader. The product was purified by silica gel flash chromatography (40 g, solids, equilibrated 0% siRNA / DCM, eluted 0% (2 CV) → 10% siRNA / DCM (20 CV)). The fraction containing the product was evaporated to dryness under vacuum. A yellow solid, 301 mg (94% yield) was obtained. MS(APCI):Chemical formula:C 34 H 31 Calculated value for NO5 (M+H) = 534; measured value: 534. 1 H NMR(400MHz,TCE) δ 10.43(s,1H), 8.63(d,J=7.9Hz,1H), 8.57(d,J=8.4Hz,1H), 8.06(d,J=2.3Hz,1H), 8.01(d,J=8.0Hz,1H), 7.62(dd,J=8.8,2.3Hz,1H), 7.37(d,J =8.7Hz,1H), 7.33(d,J=8.3Hz,1H), 6.56(s,2H), 4.38(t,J=7.0Hz,2H), 4.17(t,J=6.0Hz,2H), 2.57(s,6H), 2.25(q,J=6.6Hz,2H), 1.44(s,9H).

[0418] Compound PLC-39: Diethyl 10-(4-(3-(9-(4-(tert-butyl)phenyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)propoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-dicarboxylate Compound PLC-39 was synthesized in the same manner as for compound 32 from compound PLC-39.2 (0.275 mmol, 147 mg) and ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (0.413 mmol, 69 mg) in dried DCE (40 mL), followed by pTsOH·H2O (0.110 mmol, 21 mg), then DDQ (0.468 mmol, 106 mg), 2×Et3N (2.20 mmol, 0.31 mL), and BF3·OEt2 (3.30 mmol, 0.41 mL). The crude reaction mixture was diluted with hexane and loaded onto approximately 20 g of silica gel in a loader. The mixture was purified by silica gel flash chromatography (120 g, solids, equilibration 0% siRNA / DCM, elution 0% (2 CV) → 10% siRNA / DCM (50 CV)). The fraction containing the product was evaporated to dryness under vacuum. An orange solid, 71 mg (29% yield) was obtained. MS(APCI): Chemical formula: C 58 H 56 Calculated value (M+H) for BF2N3O8: 972; Measured value: 972. 1 H NMR(400MHz,TCE) δ 8.65(d,J=7.9Hz,1H), 8.58(d,J=8.4Hz,1H), 8.07(d,J=2.3Hz,1H), 8.03(d,J=8.1Hz, 1H), 7.62(dd,J=8.7,2.2Hz,1H), 7.36(d,J=8.7Hz,1H), 7.33(d,J=8.3Hz,1H), 6.68(s ,2H), 4.42(t,J=7.0Hz,2H), 4.28(q,J=7.1Hz,4H), 4.16(t,J=6.2Hz,2H), 2.83(s,6H) , 2.28(p,J=5.8Hz,2H), 2.05(s,6H), 1.72(s,6H), 1.44(s,9H), 1.34(t,J=7.1Hz,6H).

[0419] Synthesis of compound PLC-40 [ka]

[0420] Compound PLC-40.1:9-(6-(2-amino-4-(tert-butyl)phenoxy)-2-(2-hydroxyethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione Compound PLC-40.1 was synthesized in the same manner as described above from compound PLC-4.2 (8.827 mmol, 3.190 g), ethanolamine (17.65 mmol, 1.066 mL), and DMAP (2.648 mmol, 324 mg), followed by 200 proof ethanol (70 mL). The crude precipitate was filtered off, dissolved in acetone, and evaporated to dryness under vacuum. A yellowish-brown solid, 2.777 g (78% yield), was obtained. MS(APCI): Chemical formula: C 24 H 24 Calculated value for N2O4 (M+H) = 405; measured value: 405. 1 H NMR(400MHz,TCE) δ 8.80(dd,J=8.4,1.2Hz,1H), 8.67(dd,J=7.3,1.2Hz,1H), 8.46(d,J=8.3Hz,1H), 7.84(dd,J=8.4,7.3Hz,1H), 7.02~6.92( m,3H), 6.87(dd,J=8.4,2.3Hz,1H), 4.42(t,J=5.2Hz,2H), 3.95(t,J=5.2Hz,2H), 3.74(s,2H), 2.39(s,1H), 1.35(s,9H).

[0421] Compound PLC-40.2:9-(tert-butyl)-2-(2-hydroxyethyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione Compound PLC-40.2 was synthesized in the same manner as described above from compound PLC-40.1 (6.863 mmol, 2.776 g), NaNO2 (51.475 mmol, 3.552 g), concentrated HCl (34.317 mmol, 2.83 mL), and CuSO4·5H2O (46.67 mmol, 11.653 g). The crude product was approximately 10% acetate. This was cleaved with K2CO3 in the same manner as compound 52.2. The crudely cleaved mixture was dissolved in acetone, evaporated onto approximately 20 g of silica gel, and placed in a loader. Purification was performed by silica gel flash chromatography (120 g, solids content, equilibration 0% siRNA / DCM, elution (2 CV) → 85% siRNA / DCM (20 CV)). The fraction containing the product was evaporated to dryness under vacuum. A yellow solid, 732 mg (27% yield) was obtained. MS (APCI): Chemical formula: C 24 H 21 Calculated value for NO4 (M+H) = 388; measured value: 388.

[0422] Compound PLC-40.3: 2-(2-bromoethyl)-9-(tert-butyl)-1H-xantheno[2,1,9-def]isoquinoline-1,3(2H)-dione Compound PLC-40.3 was synthesized in the same manner as for compound 50.3 from compound PLC-40.2 (1.884 mmol, 730 mg), perbromomethane (2.826 mmol, 937 mg), and PPh3 (2.826 mmol, 741 mg) in 80 mL of dry DCM. The crude reaction mixture was loaded onto approximately 30 g of silica gel in a loader. Purification was performed by silica gel flash chromatography (120 g, solids content, equilibration 0% HCl / DCM, elution 0% (2 CV) → 15% HCl / DCM (20 CV)). The fraction containing the product was evaporated to dryness under vacuum. A yellow solid, 556 mg (44% yield) was obtained. NMR showed a purity of only about 50%. MS (APCI): Chemical formula: C 24 H 20 Calculated value (M+H) for BrNO3: 450; Measured value: 450. 1H NMR(400MHz,TCE) δ 8.62(d,J=7.9Hz,1H), 8.57(d,J=8.4Hz,1H), 8.04(d,J=2.3Hz,1H), 7.98(d,J=8.0Hz,1H), 7.62(dd,J=8.7,2. 2Hz,1H), 7.35(d,J=8.7Hz,1H), 7.31(d,J=8.4Hz,1H), 4.58(t,J=7.6Hz,2H), 3.73~3.65(m,2H), 1.44(s,9H).

[0423] Compound PLC4.4: 4-(2-(9-(tert-butyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)ethoxy)-2,6-dimethylbenzaldehyde Compound PLC-40.4 was synthesized from compound PLC-40.3 (0.450 mmol, 203 mg), 4-hydroxy-2,6-dimethylbenzaldehyde (1.350 mmol, 203 mg), and K2CO3 (1.260 mmol, 174 mg) in dry DMF (10 mL) in the same manner as described above. The crude product was filtered off, washed with water, dissolved in DCM, and evaporated to dryness. Dissolved in DCM, evaporated onto approximately 20 g of silica gel, and placed in a loader. Purified by silica gel flash chromatography (120 g, solids content, equilibrated 0% Â / DCM, eluted 0% (2 CV) → 15% Â / DCM (20 CV)). The fraction containing the product was evaporated to dryness. The reaction was repeated in the same manner. Combining both purified products yielded 64 mg of yellow solid (13% yield). MS (APCI): Chemical formula: C 33 H 29 Calculated value for NO5 (M+H) = 520; measured value: 520. 1H NMR(400MHz,TCE) δ 10.41(s,1H), 8.66(d,J=7.9Hz,1H), 8.60(d,J=8.3Hz,1H), 8.06(d,J=2.2Hz,1H), 8.01(d,J=8.0Hz,1H), 7.62(dd,J=8.7,2.2Hz,1H ), 7.36(d,J=8.7Hz,1H), 7.33(d,J=8.4Hz,1H), 6.66(s,2H), 4.64(t,J=6.2Hz,2H), 4.37(t,J=6.2Hz,2H), 2.57(s,6H), 1.44(s,9H).

[0424] Compound PLC-40: Diethyl 10-(4-(2-(9-(tert-butyl)-1,3-dioxo-1H-xantheno[2,1,9-def]isoquinoline-2(3H)-yl)ethoxy)-2,6-dimethylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabolinine-2,8-carboxylate Compound PLC-40 was synthesized in the same manner as described above from compound PLC-40.4 (0.121 mmol, 63 mg), ethyl 2,4-dimethyl-1H-pyrrole-3-carbonxylate (0.263 mmol, 44 mg) in dried DCE (20 mL), followed by pTsOH·H2O (0.0182 mmol, 4 mg), then DDQ (0.158 mmol, 36 mg), 2×Et3N (0.970 mmol, 0.140 mL), and BF3·OEt2 (1.455 mmol, 0.180 mL). The crude reaction mixture was loaded onto approximately 20 g of silica gel in a loader. The mixture was purified by silica gel flash chromatography (120 g, solids, equilibration 0% siRNA / hexane, elution 0% (2 CV) → 75% siRNA / hexane (30 CV)). The fraction containing the product was evaporated to dryness under vacuum. An orange solid, 78 mg (73% yield), was obtained. MS(APCI): Chemical formula: C 51 H 50 Calculated value (M+H) for BF2N3O8: 882; Measured value: 882. 11H NMR (400MHz, TCE) δ 8.68(d,J=7.9Hz,1H), 8.62(d,J=8.3Hz,1H), 8.07(d,J=2.3Hz,1H), 8.03( d,J=8.1Hz,1H), 7.63(dd,J=8.8,2.2Hz,1H), 7.36(t,J=8.9Hz,2H), 6.78(s ,2H), 4.66(t,J=6.5Hz,2H), 4.35(t,J=6.4Hz,2H), 4.25(q,J=7.1Hz,4H), 2.81(s,6H), 2.05(s,6H), 1.67(s,6H), 1.44(s,9H), 1.32(t,J=7.1Hz,6H).

[0425] Example 3: Manufacturing of color conversion film The glass substrate was prepared in essentially the following manner: A 1.1 mm thick glass substrate measuring 1 inch x 1 inch was cut to size. Next, the glass substrate was washed with detergent and deionized (DI) water, rinsed with fresh DI water, and sonicated for approximately 1 hour. Next, the glass was immersed in isopropanol (IPA) and sonicated for approximately 1 hour. Next, the glass substrate was immersed in acetone and sonicated for approximately 1 hour. Finally, the glass was removed from the acetone bath and dried with nitrogen gas at room temperature.

[0426] A 20 wt% solution of poly(methyl methacrylate) (PMMA) copolymer (average molecular weight 120,000 according to GPC, manufactured by MilliporeSigma, Burlington, Massachusetts, USA) in cyclopentanone (99.9% purity) was prepared. The prepared copolymer was stirred overnight at 40°C. (PMMA) CAS: 9011-14-7, (cyclopentanone) CAS: 120-92-3.

[0427] The 20% PMMA solution (4 g) prepared above was added to 3 mg of the photoluminescence complex, e.g., PLC-1 or PLC-2, prepared as described above, in a sealed container and mixed for approximately 30 minutes. Next, the PMMA / Lumiphore solution was spin-coated onto the prepared glass substrate at 1000 RPM for 20 seconds, followed by 500 RPM for 5 seconds. The resulting wet coating had a thickness of approximately 10 μm. The samples were covered with aluminum foil before spin-coating to protect them from exposure. Three samples were prepared in this manner, one for each emission / FWHM and quantum yield. The spin-coated samples were baked in a vacuum oven at 80°C for 3 hours to evaporate the remaining solvent.

[0428] A 1-inch x 1-inch sample was inserted into a Shimadzu UV-3600 UV-VIS-NIR spectrophotometer (Shimadzu Instruments, Inc., Columbia, Maryland, USA). All device operations were performed in a nitrogen-filled glove box. The absorption / emission spectra obtained for PCL-1 are shown in Figures 1 and 2, and the absorption / emission spectra obtained for PCL-2 are shown in Figure 3.

[0429] The fluorescence spectra of the 1-inch x 1-inch film samples prepared as described above were determined using a Fluorolog spectrofluorometer (Horiba Scientific, Edison, New Jersey, USA) with excitation wavelengths set to their respective maximum absorbance wavelengths. The maximum emission and FWHM are shown in Table 1.

[0430] The quantum yield of the 1-inch x 1-inch sample prepared as described above was determined by exciting it at its respective maximum absorption wavelength using a Quantarus-QY spectrophotometer (Hamamatsu Inc., Campbell, California, USA). The results are reported in Table 1.

[0431] The results of the film characterization (absorbance peak wavelength, FWHM, and quantum yield) are shown in Table 1 below.

[0432] [Table 1] [Table 2] [Table 3] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8] [Table 9] [Table 10] [Table 11] [Table 12] [Table 13] [Table 14]

Claims

1. A photoluminescent complex, The blue light absorbing portion, Linker complex and The boron-dipyromethene (BODIPY) moiety, Includes, The photoluminescent complex absorbs light energy of a first excitation wavelength and emits light energy of a second, higher wavelength, and the photoluminescent complex has an emission quantum yield of more than 80%. The blue light absorbing portion is a xanthenoisoquinoline derivative or a naphthalimide derivative. The following structure: 【Chemistry 1】 【Chemistry 2】 【Transformation 3】 【Chemistry 4】 【Transformation 5】 【Transformation 6】 【Transformation 7】 【Transformation 8】 【Chemistry 9】 【Chemistry 10】 【Chemistry 11】 【Chemistry 12】 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 【Chemistry 17】 [Chemistry 18] A photoluminescent complex that is one of the following.

2. It is a color conversion film, A transparent substrate layer, A color conversion layer containing a resin matrix, A photoluminescent complex comprising the photoluminescent complex described in claim 1 dispersed within the resin matrix, Color conversion film, including

3. The color conversion film according to claim 2, further comprising a singlet oxygen quenching agent.

4. The color conversion film according to claim 2, further comprising a free radical scavenger.

5. The color conversion film according to claim 2, wherein the color conversion film has a thickness between 10 μm and 200 μm.

6. The color conversion film according to claim 2, wherein the color conversion film absorbs light in the wavelength range of 400 nm to 480 nm and emits light in the wavelength range of 500 nm to 560 nm.

7. A method for producing a color conversion film according to any one of claims 2 to 6, Dissolving the photoluminescent complex and binder resin described in claim 1 in a solvent, The mixture is applied to one of the opposing surfaces of the transparent substrate, Methods that include...

8. A backlight unit comprising a color conversion film according to any one of claims 2 to 6.

9. A display device including the backlight unit described in claim 8.

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