Immunomodulators, compositions and methods thereof
A compound, chelate technology, applied in immunomodulators, can solve the problem of unapproved small molecule inhibitors
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment A
[0466] The preparation of embodiment A intermediate A
[0467] ((6-(Difluoromethoxy)-2-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl )phenyl)benzo[d]oxazol-5-yl)methyl)-L-proline methyl ester
[0468]
[0469] Step 1: Preparation of methyl 2,4-dihydroxy-5-nitrobenzoate
[0470]
[0471] Methyl 2,4-dihydroxybenzoate (850 g) was dissolved in glacial AcOH (3.6 L) and Ac 2 O (900mL) mixed solution. After the clear solution was cooled to 10 °C (ice bath), concentrated HNO dissolved in ice AcOH (500 mL) was added within 1 h 3 (65%). The light brown solution was warmed to 15-20°C and stirring was continued for 1 hour. Pour the reaction solution into H 2 O (3L), filter the precipitate, filter the cake with a small amount of H 2 After O washes, the crude product was poured into MeOH (2 L) with stirring, the precipitate was filtered, the filter cake was washed with a small amount of MeOH, and the title product was obtained after vacuum drying, 480 g.
[0472] St...
Embodiment B
[0493] The synthesis of embodiment B intermediate B
[0494] ((6-(difluoromethoxy)-2-(2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborin Alk-2-yl)-[1,1'-biphenyl]-3-yl)benzo[d]oxazol-5-yl)methyl)-L-proline methyl ester
[0495]
[0496] Step 1: Preparation of ((2-(3'-bromo-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-6-(difluoromethoxy)benzo[ d] oxazol-5-yl)methyl)-L-proline methyl ester
[0497]
[0498] in N 2 To a solution of Intermediate A (21.7 g), 1-bromo-3-iodo-2-toluene (9.0 g) in toluene (150 mL) was added EtOH (30 mL), 10% Na 2 CO 3 aq.(30mL) and Pd(dppf)Cl 2 .DCM (1.0g). The mixture was stirred overnight at 90 °C. Reaction with H 2 Quenched with O (100 mL) and extracted 3 times with EtOAc (100 mL). The organic phases were combined and washed with brine. The resulting solution was concentrated and purified by column chromatography to obtain ((2-(3'-bromo-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-6-(difluoro Methoxy)benzo[d]oxazol-5-yl)methyl)-L-proline methyl ...
Embodiment 1
[0502] The preparation of embodiment 1 compound 1
[0503] ((6-(difluoromethoxy)-2-(3'-(6-(difluoromethoxy)-5-((((1R,2S)-2-hydroxycyclopentyl)(methyl )amino)methyl)benzo[d]oxazol-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)benzo[d]oxazole- 5-yl)methyl)-L-proline
[0504]
[0505] Compound 1
[0506] Step 1: Preparation of ((6-(difluoromethoxy)-2-(3'-(6-(difluoromethoxy)-5-(hydroxymethyl)benzo[d]oxazole-2- base)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)benzo[d]oxazol-5-yl)methyl)-L-proline methyl ester
[0507]
[0508] To the 1,4-dioxane (80mL) / H of intermediate A (5g) 2 O (16mL) solution was added compound a-6 (3.9g), K 2 CO 3 (3.8g) and Pd(dppf)Cl 2 CH 2 Cl 2 (732 mg). Mixture in N 2 Stir at 80°C for 12hrs under protection. Almost complete reaction to raw material and reaction stops, and the mixture is poured into H 2 O (300 mL) and extracted 3 times with DCM (100 mL). The organic phase was washed with brine, anhydrous Na 2 SO 4 Dry, filter and concentrate to gi...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More