Water → 5-[(3As,4s,6ar)-2-oxohexahydro-1h-thieno[3,4-d]imidazol-4-yl]-n-(4-{[3-[2-(cyclopentylamino)-pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]amino}butyl)-pentanamide

HRID 861165ノート

反応式

HRID 861165 の反応式
[CH:1]1([NH:6][C:7]2[N:12]=[C:11]([C:13]3[C:14]([C:28]4[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=4)=[N:15][N:16]4[C:21]([NH:22][CH2:23][CH2:24][CH2:25][CH2:26][NH2:27])=[CH:20][CH:19]=[CH:18][C:17]=34)[CH:10]=[CH:9][N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.C1C(=O)N([O:50][C:51]([CH2:53][CH2:54][CH2:55][CH2:56][C@@H:57]2[S:61][CH2:60][C@@H:59]3[NH:62][C:63]([NH:65][C@H:58]23)=[O:64])=O)C(=O)C1.O>CN(C)C=O>[O:64]=[C:63]1[NH:62][C@H:59]2[CH2:60][S:61][C@@H:57]([CH2:56][CH2:55][CH2:54][CH2:53][C:51]([NH:27][CH2:26][CH2:25][CH2:24][CH2:23][NH:22][C:21]3[N:16]4[N:15]=[C:14]([C:28]5[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=5)[C:13]([C:11]5[CH:10]=[CH:9][N:8]=[C:7]([NH:6][CH:1]6[CH2:2][CH2:3][CH2:4][CH2:5]6)[N:12]=5)=[C:17]4[CH:18]=[CH:19][CH:20]=3)=[O:50])[C@H:58]2[NH:65]1

参加物

6

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 6710714Biotin N-hydroxysuccinimide ester2 回HCID 10140154N-[3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]butane-1,4-diamine

生成物 1

HCID 574947285-[(3As,4s,6ar)-2-oxohexahydro-1h-thieno[3,4-d]imidazol-4-yl]-n-(4-{[3-[2-(cyclopentylamino)-pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]amino}butyl)-pentanamide収率 51.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a cold (0° C.) solution of N-[3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]butane-1,4-diamine (33 mg, 0.07 mmol) in N,N-dimethylformamide (3 mL) was added triethylamine (0.03 mL, 0.21 mmol) and d-biotin-N-hydroxysuccinimide ester (27 mg, 0.08 mmol). The resultant mixture was warmed to room temperature and stirred for 30 minutes. A subsequent 5 mg of d-biotin-N-hydroxysuccinimide ester was added and the mixture was stirred an additional 30 minutes. Water was added and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate and then brine. The aqueous layer was extracted with dichloromethane and the combined organics were dried over sodium sulfate. Filtration and concentration followed by flash chromatography (5% to 8% methanol in dichloromethane) provided 5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-N-(4-{[3-[2-(cyclopentylamino)-pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]amino}butyl)-pentanamide (25 mg, 51%) as a yellow solid. 1H NMR (CDCl3): δ 7.98 (d, 1 H), 7.80 (d, 1 H), 7.58 (d, 2 H), 7.32 (m, 1 H), 7.00 (d, 2 H), 6.60 (s,1 H), 6.39 (m, 1 H), 6.33 (d, 1 H), 6.18 (m, 1 H), 6.02 (m, 1 H), 5.72 (s, 1 H), 5.62 (broad, 1 H), 4.44–4.31 (m, 2 H), 4.19 (m, 1 H), 3.89 (s, 3 H), 3.39 (m, 2 H), 3.28 (m, 2 H), 3.06 (m, 1 H), 2.95 (m, 2 H), 2.77 (dd, 1 H), 2.58 (d, 1 H), 2.20–2.05 (m, 4 H), 1.82–1.54 (m, 12 H), 1.39 (m, 2 H); MS m/z 698 (M+1).

後処理

  1. stirringthe mixture was stirred an additional 30 minutes
  2. customthe layers were separated
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate
  4. extractionThe aqueous layer was extracted with dichloromethane
  5. dry with materialthe combined organics were dried over sodium sulfate
  6. filtrationFiltration and concentration

出典と根拠

ORDレコード
ord-f1866283030c4ddb819d4d99b87ef169
出典データセット
uspto-grants-2006_12
特許番号
US07153855B2

反応ノート

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