2-Pyrazinecarboxylic acid → N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)pyrazine-2-carboxamide

HRID 1410018노트

반응식

HRID 1410018 반응식
Cl.[NH2:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH3:27])[CH:19]=3)[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=2)[CH2:4]1.[N:28]1[CH:33]=[CH:32][N:31]=[CH:30][C:29]=1[C:34](O)=[O:35].CCN=C=NCCCN(C)C.CN1C=CN=C1>C(Cl)Cl>[CH3:27][O:26][C:20]1[CH:19]=[C:18]([NH:17][C:10]2[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=[C:8]([N:5]3[CH2:6][CH2:7][CH:3]([NH:2][C:34]([C:29]4[CH:30]=[N:31][CH:32]=[CH:33][N:28]=4)=[O:35])[CH2:4]3)[N:9]=2)[CH:23]=[CH:22][C:21]=1[O:24][CH3:25]

참가 물질

6

반응물 4

HCID 10472-Pyrazinecarboxylic acidHCID 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 683792715-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride

생성물 1

HCID 66551739N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)pyrazine-2-carboxamide수율 73.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A mixture of 5-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride (40 mg, 0.1 mmol), pyrazine-2-carboxylic acid (14 mg, 0.11 mmol), EDCI (38 mg, 0.2 mmol) and N-methylimidazole (25 mg, 0.3 mmol) in 3 mL of DCM was stirred at room temperature for 15 hours. The mixture was washed with water (5 mL), the organic layer was dried over Na2SO4. After filtration and concentration, the residue was purified by preparative TLC (Silica gel, 20 cm×20 cm, separated by EtOAc, eluted by DCM:MeOH=1:20, v/v) to give N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)pyrazine-2-carboxamide (35 mg, 73%) as white solid. 1H NMR (300 MHz, DMSO): δ 9.56 (s, 1H), 9.18 (s, 1H), 9.12 (d, 1H, J=7.8 Hz), 8.86 (d, 1H, J=2.4 Hz), 8.80 (s, 1H), 8.71 (s, 1H), 7.85 (s, 1H), 7.50-7.27 (m, 1H), 6.90 (d, 1H, J=8.4 Hz), 4.64-4.62 (m, 1H), 3.75-3.64 (m, 10H), 2.27-2.16 (m, 2H). LC-MS: 479 [M+H]+, 477 [M−H]−, tR=1.39 min. HPLC: 97.06% at 214 nm, 96.92% at 254 nm, tR=4.63 min.

후처리

  1. washThe mixture was washed with water (5 mL)
  2. dry with materialthe organic layer was dried over Na2SO4
  3. filtrationAfter filtration and concentration
  4. customthe residue was purified by preparative TLC (Silica gel, 20 cm×20 cm, separated by EtOAc, eluted by DCM:MeOH=1:20, v/v)

출처 및 근거

ORD 기록
ord-6dcb309198104244a3192d02132dac8b
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921383B2

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