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 494074Notes

Reaction equation

HRID 494074 reaction equation
[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

Participants

6

Reactant 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

Product 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-carboxamideYield 72.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-0a628520b8e445c688dcabbb656b4dce
Source dataset
uspto-grants-2009_05
Patent number
US07538102B2

Reaction notes

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