1-Hydroxybenzotriazole → HCID 178523103, compound

HRID 1453390Notes

Reaction equation

HRID 1453390 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39]([OH:41])=O)=[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.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:73][CH2:74][C:75]1[NH:79][N:78]=[N:77][N:76]=1>C(Cl)Cl>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39]([NH:73][CH2:74][C:75]4[NH:79][N:78]=[N:77][N:76]=4)=[O:41])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:23]4[CH2:24][CH2:25][CH:26]([N:29]5[CH2:30][CH2:31][O:32][CH2:33][CH2:34]5)[CH2:27][CH2:28]4)=[O:22])=[CH:18][C:17]4[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 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 acidHCID 178510704HCID 178510704, compound

Product 1

HCID 178523103HCID 178523103, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 (135 mg, 0.24 mmol) in CH2Cl2 (1 mL) were added N,N-diisopropylethylamine (170 μL, 0.98 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (64 mg, 0.33 mmol), 1-hydroxybenzotriazole (47 mg, 0.35 mmol), and 5-(aminomethyl)tetrazole (33 mg, 0.33 mmol). The suspension was allowed to stir at r.t. for 23 hr, filtered through Celite, and chromatographed on silica gel (gradient elution: 0%→30% MeOH in CH2Cl2) to afford the title compound as a yellow solid (70 mg, 46% yield). LC/MS (ESI) retention time: 1.61 min, m/z 635 (MH+); 1H NMR (400 MHz, CD3OD) δ 1.08-1.23 (m, 1 H) 1.35-1.48 (m, 4 H) 1.66 -1.79 (m, 3 H) 1.86 -1.92 (m, 1 H) 1.96 -2.14 (m, 3 H) 2.44-2.60 (m, 5 H) 2.74 -2.89 (m, 2 H) 3.16 (dd, J=7.55 Hz, 1 H) 3.57 -3.73 (m, 5 H) 4.25 (s, 1 H) 4.94-5.08 (m, 1 H) 6.87 (s, 1 H) 7.43-7.51 (m, 3 H) 7.52-7.59 (m, 2 H) 7.83 (d, J=8.56 Hz, 1 H) 8.11 (s, 1 H).

Workup

  1. filtrationfiltered through Celite
  2. customchromatographed on silica gel (gradient elution: 0%→30% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-371f3549cb3244c78de5e6e969459ddd
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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