1-Hydroxybenzotriazole → HCID 16667212, compound

HRID 1453393Notes

Reaction equation

HRID 1453393 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.[NH2:42][CH2:43][C:44]1[CH:49]=[N:48][C:47]([CH3:50])=[CH:46][N:45]=1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39]([NH:42][CH2:43][C:44]4[CH:49]=[N:48][C:47]([CH3:50])=[CH:46][N:45]=4)=[O:41])=[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[CH2:30][CH2:31][O:32][CH2:33][CH2:34]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)[CH2:2][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 27564962-(Aminomethyl)-5-methylpyrazineHCID 5752668313-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

Product 1

HCID 16667212HCID 16667212, compoundYield 93.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 13-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (40 mg, 0.07 mmol), 2-(aminomethyl)-5-methylpyrazine (12 mg, 0.1 mmol), N,N-diisopropylethylamine (60 μL, 0.34 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (19 mg, 0.1 mmol), and 1-hydroxybenzotriazole (14 mg, 0.1 mmol) in CH2Cl2 (1.5 mL) was stirred at r.t. for 20 h, at which point it was introduced directly to silica gel and chromatographed (gradient elution: 0%→10% MeOH in CH2Cl2) to afford a yellow foam, which was triturated with Et2O and dried to give the title compound as a pale yellow solid (43 mg, 90% yield). LC/MS (ESI) retention time: 1.69 min, m/z 659 (MH+); 1H NMR (400 MHz, CDCl3) δ 1.28-1.44 (m, 3 H) 1.46-1.59 (m, 1 H) 1.61-1.70 (m, 1 H) 1.71-1.81 (m, 2 H) 1.85-1.96 (m, 1 H) 1.97-2.13 (m, 3 H) 2.29 (t, J=10.45 Hz, 1 H) 2.35-2.46 (m, 4 H) 2.55 (s, 3 H) 2.61-2.77 (m, 2 H) 2.77-2.89 (m, 2 H) 3.62 (s, 4 H) 4.38 (s, 1 H) 4.78 (d, J=5.04 Hz, 2 H) 5.00-5.18 (m, 1 H) 6.81 (s, 1 H) 7.32-7.40 (m, 2 H) 7.40-7.50 (m, 3 H) 7.51-7.59 (m, 1 H) 7.88 (d, J=8.56 Hz, 1 H) 8.01 (s, 1 H) 8.39 (s, 1 H) 8.56 (d, J=1.01 Hz, 1 H); 13C NMR (101 MHz, CDCl3) δ 21.18, 26.21, 27.03, 28.08, 33.26, 36.73, 41.91, 42.60, 49.52, 61.59, 67.07, 108.98, 116.90, 120.03, 121.21, 126.98, 127.94, 128.21, 129.27, 130.96, 131.23, 133.27, 134.01, 135.18, 135.25, 136.39, 142.94, 143.40, 149.41, 152.50, 168.10, 168.87.

Workup

  1. additionwas introduced directly to silica gel
  2. customchromatographed
  3. wash(gradient elution: 0%→10% MeOH in CH2Cl2)
  4. customto afford a yellow foam, which
  5. customwas triturated with Et2O
  6. customdried

Sources & evidence

ORD record
ord-07ec297ec1524cf0aeba415dd27f0a90
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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