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

HRID 1410018ノート

反応式

HRID 1410018 の反応式
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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-6dcb309198104244a3192d02132dac8b
出典データセット
uspto-grants-2014_12
特許番号
US08921383B2

反応ノート

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