Bromodomain inhibitor compounds and uses thereof
A compound and drug technology, applied in the field of bromodomain inhibitor compounds
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0105] Embodiment 1: the preparation of intermediate 1-6
[0106]
[0107] Synthesis of Compound 1-2:
[0108] 3-Methyl-1H-pyrrole-2-carboxylic acid ethyl ester (I-1) (2.298 g, 15 mmol) was dissolved in 8 mL of N-methylpyrrolidone and 2-bromo-1,1-diethoxyethane ( To the mixture of 3.843 g, 19.5 mmol), 60% sodium hydride (720 mg, 18 mmol) was added in portions at room temperature. The solution was heated to 130° C. for 5 hours under the protection of argon and then cooled to room temperature. The solution was diluted with water, extracted, dried, concentrated, and purified by silica gel column chromatography to obtain compound I-2 as a white solid (2.7 g). HPLC-MS: [M+H] + = 270.1.
[0109] Synthesis of Compound 1-3:
[0110] Compound I-2 (2.7g, 10mmol) was dissolved in 60mL ethanol / water 1:1 mixed solution, lithium hydroxide monohydrate (2.402g, 57mmol) was added, heated to 75°C overnight and cooled to room temperature. Ethanol was removed by rotary evaporation in vac...
Embodiment 2
[0117] Embodiment 2: the preparation of intermediate II-5
[0118]
[0119] Synthesis of compound II-2:
[0120] Compound I-1 (1.6g, 10mmol) was dissolved in 60mL ethanol / water 1:1 mixed solution, lithium hydroxide monohydrate (2.402g, 57mmol) was added, heated to 75°C overnight and cooled to room temperature. Vacuum rotary evaporation to remove ethanol, dilute with water, add 2M hydrochloric acid solution, and extract with ethyl acetate, combine organic layers, dry over anhydrous sodium sulfate, vacuum rotary evaporation to remove ethyl acetate to obtain compound II-2 as a colorless oil (1.562g). HPLC-MS: [M-H] + = 124.1.
[0121] Synthesis of Compound II-3:
[0122] Compound II-2 (1.562g, 12.5mmol), 2-chloroethylamine hydrochloride (1.882g, 16.2mmol) and HATU (6.170g, 16.2mmol) were dissolved in 50mL of dichloromethane, 5.2mL of DIPEA was added, After reacting at room temperature for 2 hours, 100 mL of saturated aqueous sodium bicarbonate was added, extracted with di...
Embodiment 3
[0127] Embodiment 3: the preparation of intermediate III-4
[0128]
[0129] Synthesis of compound III-2:
[0130] LiHMDS (2.5 mL, 1M in THF) was slowly dropped into a solution of compound I-1 (309 mg, 2 mmol) in anhydrous DMF (30 mL) at -10 °C. After stirring for 10 minutes, the solution was moved to 0°C, and diphenylphosphonohydroxylamine (0.56 g, 2.4 mmol) was added, and stirred for 5 hours. After the reaction was completed, water was added to quench until a clear solution was formed. The solvent was removed by rotary evaporation in vacuo, and purified by silica gel column chromatography to obtain compound III-2 (220 mg) as a white solid. HPLC-MS: [M+H] + = 169.2.
[0131] Synthesis of Compound III-3:
[0132] Compound III-2 (295 mg, 1.7 mmol) was dissolved in 3 mL of formamide, placed in a sealed tube and heated to 180°C, reacted overnight, an off-white solid precipitated, cooled to room temperature, filtered, and washed with ethyl acetate to obtain compound III -...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More