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

HRID 1453397

반응식

HRID 1453397 반응식
[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.C(O)(=O)C.[NH2:55][CH2:56][C:57]([N:59]([CH3:61])[CH3:60])=[O:58].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:55][CH2:56][C:57]([N:59]([CH3:61])[CH3:60])=[O:58])=[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[CH2:34][CH2:33][O:32][CH2:31][CH2:30]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

참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 533990092-Amino-N,N-dimethylacetamide acetateHCID 5752668313-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

생성물 1

HCID 5752671313-cyclohexyl-N-[2-(dimethylamino)-2-oxoethyl]-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamide수율 49.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a stirred 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) in CH2Cl2 (1.5 mL) were added N,N-diisopropylethylamine (60 μL, 0.34 mmol), 2-amino-N,N-dimethylacetamide monoacetate (16 mg, 0.1 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (19 mg, 0.1 mmol), and 1-hydroxybenzotriazole (14 mg, 0.1 mmol). The suspension was allowed to stir at r.t. for 2 days, then diluted with CH2Cl2, filtered through Celite, and chromatographed on silica gel (gradient elution: 0%→10% MeOH in CH2Cl2) to give the title compound as a yellow solid (22 mg, 48% yield). LC/MS (ESI) retention time: 1.66 min, m/z 638 (MH+); 1H NMR (400 MHz, CDCl3) δ 1.29-1.43 (m, 2 H) 1.47-1.59 (m, 1 H) 1.71-1.80 (m, 2 H) 1.87-1.96 (m, 1 H) 2.34-2.35 (m, 1 H) 2.40-2.51 (m, 3 H) 2.60-2.76 (m, 2 H) 2.77-2.89 (m, 1 H) 3.02 (s, 3 H) 3.04 (s, 3 H) 3.66 (s, 4 H) 4.25 (d, J=3.78 Hz, 2 H) 4.39 (s, 1 H) 5.07-5.08 (m, 1 H) 6.61 (s, 1 H) 6.81 (s, 1 H) 7.33-7.49 (m, 5 H) 7.51-7.59 (m, 1 H) 7.86 (d, J=8.56 Hz, 1 H) 8.02 (s, 1 H).

후처리

  1. filtrationfiltered through Celite
  2. customchromatographed on silica gel (gradient elution: 0%→10% MeOH in CH2Cl2)

출처 및 근거

ORD 기록
ord-565b966a86424b09af6d6b2746117a5a
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07473688B2

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