Method for preparing protein deacetylase inhibitors
A compound and reaction technology, applied in the field of compound preparation, can solve the problems of loss of intermediates, impractical industrial expansion of synthetic routes, and unscalable problems
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
example
[0168] Instruments and methods
[0169] Differential scanning calorimetry (DSC) data was collected using a TA Instruments Q10DSC. Roughly, samples (2-8 mg) were placed in unsealed, but covered, airtight chromate anodized (alodined) aluminum sample pans and heated at 10 °C / min under a nitrogen purge of 50 mL / min. The scan was performed from 30°C to 300°C at a rate of (minutes).
[0170] Thermogravimetric analysis (TGA) data was collected using a TA Instruments TGA Q500. Roughly, 5-10 mg of sample was placed in an open pre-tared aluminum sample pan and scanned from 25°C to 300°C at a rate of 10°C / min using a nitrogen purge of 60 mL / min.
[0171] X-ray powder diffractometer (XRPD) patterns were obtained using a Bruker D8 Advance equipped with a Cu Kα radiation source (λ = 1.54°A), a 9-position sample holder and a LYNXEYE ultrafast detector. Samples were analyzed on a background-free silicon wafer holder.
[0172] Dynamic vapor sorption (DVS) analysis was performed using an ...
example 1
[0177] Example 1: Comparison of 2-(diphenylamino)-N-(7-(hydroxylamino)-7-oxoheptyl)pyrimidine-5-formamide become
[0178] Reaction scheme
[0179]
[0180] Synthesis of intermediate 2: aniline (3.7g, 40mmol), compound 1 (7.5g, 40mmol) and K 2 CO 3 (11g, 80mmol) in DMF (100ml) was degassed and heated at 120°C under N 2 Stir overnight. The reaction mixture was cooled to room temperature and diluted with EtOAc (200ml), then washed with saturated brine (200ml x 3). The organic layer was separated and washed with Na 2 SO 4 Drying, evaporation to dryness and purification by silica gel chromatography (petroleum ether / EtOAc=10 / 1) gave the desired product (6.2 g, 64%) as a white solid.
[0181] Synthesis of Intermediate 3: Compound 2 (6.2g, 25mmol), iodobenzene (6.12g, 30mmol), CuI (955mg, 5.0mmol), Cs 2 CO 3 (16.3g, 50mmol) in TEOS (200ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140°C for 14 hours. After cooling to room temperatur...
example 2
[0185] Example 2: 2-((2-Chlorophenyl)(phenyl)amino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-formyl Comparative synthesis of amine-compound (I)
[0186] Reaction scheme
[0187]
[0188] step 1)
[0189] Synthesis of Intermediate 2: Aniline (3.7g, 40mmol), ethyl 2-chloropyrimidine-5-carboxylate 1 (7.5g, 40mmol), K 2 CO 3 (11g, 80mmol) in DMF (100ml) was degassed and heated at 120°C under N 2 Stir overnight. The reaction mixture was cooled to room temperature and diluted with EtOAc (200ml), then washed with saturated brine (200ml x 3). The organic layer was separated and washed with Na 2 SO 4 Drying, evaporation to dryness and purification by silica gel chromatography (petroleum ether / EtOAc=10 / 1) gave the desired product (6.2 g, 64%) as a white solid.
[0190] step (2)
[0191] Synthesis of Intermediate 3: Compound 2 (69.2g, 1 equivalent), 1-chloro-2-iodobenzene (135.7g, 2 equivalents), Li 2 CO 3 (42.04g, 2 equivalents), K 2 CO 3 (39.32 g, 1 equiv),...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More