1-Hydroxybenzotriazole → N-(1H-benzimidazol-2-ylmethyl)-13-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 1453389

Reaction equation

HRID 1453389 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39](O)=[O:40])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:23]4[CH2:28][CH2:27][CH:26]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:25][CH2:24]4)=[O:22])=[CH:18][C:17]4[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O.Cl.Cl.[NH2:45][CH2:46][C:47]1[NH:48][C:49]2[CH:55]=[CH:54][CH:53]=[CH:52][C:50]=2[N:51]=1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C=O)C>[NH:48]1[C:49]2[CH:55]=[CH:54][CH:53]=[CH:52][C:50]=2[N:51]=[C:47]1[CH2:46][NH:45][C:39]([C:11]1[CH:10]=[CH:9][C:8]2[C:7]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[C:15]3[C:16]4[CH:38]=[CH:37][CH:36]=[CH:35][C:17]=4[CH:18]=[C:19]([C:21]([N:23]4[CH2:28][CH2:27][CH:26]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:25][CH2:24]4)=[O:22])[CH2:20][N:14]3[C:13]=2[CH:12]=1)=[O:40]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 145819Benzimidazol-2-ylmethylamine dihydrochloride hydrateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5752668313-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

Product 1

HCID 57526621N-(1H-benzimidazol-2-ylmethyl)-13-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamideYield 14.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 13-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (134 mg, 0.24 mmol) in DMF (500 μL) were added 2-aminomethyl benzimidazole dihydrochloride hydrate (75 mg, 0.32 mmol), N,N-diisopropylethylamine (165 μL, 0.95 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (60 mg, 0.31 mmol), and 1-hydroxybenzotriazole (44 mg, 0.33 mmol). The suspension was allowed to stir at r.t. for 4 hr, at which point the solvent was removed under reduced pressure. CH2Cl2 (5 mL) was added, and the suspension filtered through Celite, and chromatographed on silica gel (gradient elution: 0%→10% MeOH in CH2Cl2) to afford the title compound as a pale yellow solid (24 mg, 14% yield). LC/MS (ESI) retention time: 1.57 min, m/z 683 (MH+); 1H NMR (400 MHz, CDCl3) δ 1.07-1.53 (m, 4 H) 1.63-1.78 (m, 3 H) 1.99 (s, 4 H) 2.25 (t, J=11.08 Hz, 1 H) 2.39 (s, 4 H) 2.59-2.87 (m, 3 H) 3.63 (s, 4 H) 4.14 (s, 1 H) 4.73-5.00 (m, 3 H) 6.78 (s, 1 H) 7.17 (ddd, J=9.63, 3.90, 3.59 Hz, 2 H) 7.34 (dd, J=7.05, 1.76 Hz, 1 H) 7.40-7.47 (m, 2 H) 7.50-7.58 (m, 4 H) 7.73 (d, J=8.31 Hz, 1 H) 8.16 (s, 1 H) 8.68 (s, 1 H).

Workup

  1. customwas removed under reduced pressure
  2. additionCH2Cl2 (5 mL) was added
  3. filtrationthe suspension filtered through Celite
  4. customchromatographed on silica gel (gradient elution: 0%→10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-55b19d1be6cb4263af529b201683426b
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Linked notes

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