1-Methylimidazole → N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide

HRID 1410020ノート

反応式

HRID 1410020 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.[O:28]=[C:29]1[NH:33][C:32]2[CH:34]=[CH:35][C:36]([C:38](O)=[O:39])=[CH:37][C:31]=2[NH:30]1.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:38]([C:36]4[CH:35]=[CH:34][C:32]5[NH:33][C:29](=[O:28])[NH:30][C:31]=5[CH:37]=4)=[O:39])[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 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 7807572-oxo-2,3-dihydro-1H-1,3-benzodiazole-5-carboxylic acidHCID 683792715-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride

生成物 1

HCID 66551741N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide収率 19.2%

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 (100 mg, 0.245 mmol), 2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carboxylic acid (48 mg, 0.27 mmol), EDCI (97 mg, 0.49 mmol) and N-methylimidazole (60 mg, 0.735 mmol) in 10 mL of DCM was stirred at room temperature for 16 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 column chromatography on silica gel eluting with a mixture of CH2Cl2 and methanol (100:1: to 20:1, V/V) to give N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide (25 mg, 19%) as white solid. 1H NMR (300 MHz, DMSO): δ 9.57 (s, 1H), 8.81 (s, 1H), 8.475-8.46 (m, 1H), 8.27-8.25 (m, 2H), 7.60-7.25 (m, 2H), 6.92 (d, 1H, J=8.7 Hz), 6.47-6.39 (m, 3H), 4.54-4.52 (m, 1H), 3.76-3.58 (m, 10H), 2.27-2.05 (m, 2H). LC-MS: 247 [M/2+H]+, 493 [M+H]+, 491 [M−H]−, tR=1.22 min. HPLC: 95.20% at 214 nm, 95.06% at 254 nm, tR=5.64 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 column chromatography on silica gel eluting with a mixture of CH2Cl2 and methanol (100:1: to 20:1, V/V)

出典と根拠

ORDレコード
ord-e9065dd496a14957854d9093b5e1047d
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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