4-(3-(1,4-Diazepan-1-yl)propyl)morpholine → 13-cyclohexyl-N-(cyclopropylsulfonyl)-3-methoxy-6-((4-(3-(4-morpholinyl)propyl)-1,4-diazepan-1-yl)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 494074ノート

反応式

HRID 494074 の反応式
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:30](=[O:38])[NH:31][S:32]([CH:35]4[CH2:37][CH2:36]4)(=[O:34])=[O:33])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([OH:23])=O)=[CH:18][C:17]4[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:39]1([CH2:46][CH2:47][CH2:48][N:49]2[CH2:54][CH2:53][O:52][CH2:51][CH2:50]2)[CH2:45][CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CO>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:30]([NH:31][S:32]([CH:35]4[CH2:36][CH2:37]4)(=[O:34])=[O:33])=[O:38])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:42]4[CH2:43][CH2:44][CH2:45][N:39]([CH2:46][CH2:47][CH2:48][N:49]5[CH2:50][CH2:51][O:52][CH2:53][CH2:54]5)[CH2:40][CH2:41]4)=[O:23])=[CH:18][C:17]4[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

参加物

6

反応物 3

HCID 27375254-(3-(1,4-Diazepan-1-yl)propyl)morpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 5755909613-cyclohexyl-10-((cyclopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid

生成物 1

HCID 5768245813-cyclohexyl-N-(cyclopropylsulfonyl)-3-methoxy-6-((4-(3-(4-morpholinyl)propyl)-1,4-diazepan-1-yl)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide収率 72.6%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a stirring solution of 13-cyclohexyl-10-((cyclopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid (33 mg, 0.062 mmol) and 4-(3-(1,4-diazepan-1-yl)propyl)morpholine (36 mg, 0.158 mmol) in DMF (0.5 ml) and TEA (50 μl, 0.359 mmol) was added HATU (35 mg, 0.092 mmol). The reaction mixture was stirred at room temperature under nitrogen for 4 h. The crude reaction mixture was diluted with MeOH (˜1 mL), filtered and purified by preparative HPLC (H2O/CH3CN with 10 mM NH4OAc) to yield 13-cyclohexyl-N-(cyclopropylsulfonyl)-3-methoxy-6-((4-(3-(4-morpholinyl)propyl)-1,4-diazepan-1-yl)carbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide (35.1 mg, 0.045 mmol, 72.6% yield) as a yellow solid. 1HNMR (300 MHz, CD3OD) δ 0.91-2.34 (m, 20H), 2.49-3.49 (m, 15H), 3.81-3.96 (m, 7H), 4.03-4.23 (m, 1H), 4.30-4.48 (m, 1H), 5.05-5.23 (m, 1H), 6.90 (s, 1H) 7.04 (d, J=2.6 Hz, 1H), 7.13 (dd, J=8.4, 2.6 Hz, 1H), 7.53 (d, J=8.4 Hz, 1H), 7.42-7.88 (m, 2H), 8.24 (s, 1H). LCMS: m/e 744 (M+H)+, ret time 2.88 min, column B, 4 minute gradient.

後処理

  1. customThe crude reaction mixture
  2. filtrationfiltered
  3. custompurified by preparative HPLC (H2O/CH3CN with 10 mM NH4OAc)

出典と根拠

ORDレコード
ord-0a628520b8e445c688dcabbb656b4dce
出典データセット
uspto-grants-2009_05
特許番号
US07538102B2

反応ノート

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