1-(t-Butoxycarbonyl)-3-(chloromethyl)-6-nitroindoline → 2-[[3-(chloromethyl)-6-nitroindolin-1-yl]carbonyl]-N-[2-(4-morpholinyl)ethyl]indole-6-carboxamide

HRID 1603045Notes

Reaction equation

HRID 1603045 reaction equation
C(O[C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([N+:17]([O-:19])=[O:18])[CH:15]=2)[CH:10]([CH2:20][Cl:21])[CH2:9]1)=[O:7])(C)(C)C.C([C:25]1[NH:26][C:27]2[C:32]([CH:33]=1)=[CH:31][CH:30]=[C:29]([C:34]([NH:36][CH2:37][CH2:38][N:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1)=[O:35])[CH:28]=2)(O)=O>>[Cl:21][CH2:20][CH:10]1[C:11]2[C:16](=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)[N:8]([C:6]([C:25]2[NH:26][C:27]3[C:32]([CH:33]=2)=[CH:31][CH:30]=[C:29]([C:34]([NH:36][CH2:37][CH2:38][N:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[O:35])[CH:28]=3)=[O:7])[CH2:9]1

Participants

3

Reactant 2

HCID 108289531-(t-Butoxycarbonyl)-3-(chloromethyl)-6-nitroindolineHCID 196087772-carboxy-N-[2-(4-morpholinyl)ethyl]indole-6-carboxamide

Product 1

HCID 3899042-[[3-(chloromethyl)-6-nitroindolin-1-yl]carbonyl]-N-[2-(4-morpholinyl)ethyl]indole-6-carboxamideYield 50%

Procedure

1-(t-Butoxycarbonyl)-3-(chloromethyl)-6-nitroindoline was coupled with 2-carboxy-N-[2-(4-morpholinyl)ethyl]indole-6-carboxamide by the method described above and triturated with hot MeOH to give 2-[[3-(chloromethyl)-6-nitroindolin-1-yl]carbonyl]-N-[2-(4-morpholinyl)ethyl]indole-6-carboxamide as a yellow solid (50%), mp 227-228° C. (dec.). 1H NMR [(CD3)2SO] δ12.15 (s, 1H, indole NH), 8.98 (d, J=2.0 Hz, 1H, H-7), 8.41 (t, J=5.5 Hz, 1H, amide NH), 8.04 (dd, J=8.3, 2.2 Hz, 1H, H-5), 8.01 (s, 1 H, H-3' or H-7'), 7.76 (d, J=8.2 Hz, 1H, H-4 or H-4'), 7.74 (d, J=8.0 Hz, 1H, H-4 or H-4'), 7.57 (dd, J=8.5, 1.1 Hz, 1H, H-5'), 7.28 (d, J=1.4 Hz, 1H, H-3' or H-7'), 4.86 (t, J=10.1 Hz, 1H, H-2), 4.51 (dd, J=10.7, 5.2 Hz, 1H, H-2), 4.19-4.06 (m, 3H, H-3 and CH2Cl), 3.59 (t, J=4.5 Hz, 4H, CH2O), 3.42 (q, J=6.5 Hz, 2H, CONHCH2), 2.50 (t, J=6.9 Hz, 2H, CONHCH2CH2), 2.46-2.41 (m, 4H, NCH2CH2O); 13C NMR δ166.7 (CONH), 160.4 (CON), 147.6, 144.6, 144.0, 135.7, 131.8, 130.8, 129.0 (C-6,8,9,2',6',8',9'), 125.5, 121.6, 119.5, 118.9, 112.0, 111.2, 106.1 (C-4,5,7,3',4',5',7'), 66.2 (CH2O), 57.4 (CONHCH2CH2), 54.0 (C-2), 53.3 (NCH2CH2O), 47.0 (CH2Cl), 42.0 (C-3), 36.6 (CONHCH2). A sample was converted to the hydrochloride salt and triturated with hot EtOH to give 2-[[3-(chloromethyl)-6-nitroindolin-1-yl]carbonyl]-N-[2-(4-morpholinyl)ethyl]indole-6-carboxamide hydrochloride as a pale yellow powder, mp 280-285° C. (dec.). Anal. (C25H26ClN5O5.HCl.H2O) C,H,N.

Workup

  1. customtriturated with hot MeOH

Sources & evidence

ORD record
ord-16d575ac9f364792967444c458cd987e
Source dataset
uspto-grants-1999_11
Patent number
US05985909

Reaction notes

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