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

HRID 1453392노트

반응식

HRID 1453392 반응식
[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.C(N(CC)C(C)C)(C)C.Cl.Cl.[NH2:53][CH2:54][C:55]1[N:56]=[C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][N:58]2[CH:63]=1.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:53][CH2:54][C:55]4[N:56]=[C:57]5[CH:62]=[CH:61][CH:60]=[CH:59][N:58]5[CH:63]=4)=[O:40])=[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 2771120Imidazo[1,2-a]pyridin-2-ylmethanamine dihydrochlorideHCID 5752668313-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

생성물 1

HCID 1666716713-cyclohexyl-N-(imidazo[1,2-a]pyridin-2-ylmethyl)-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamide수율 35%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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 (70 mg, 0.13 mmol) in CH2Cl2 (1 mL) were added N,N-diisopropylethylamine (85 μL, 0.49 mmol), 2-aminomethylimidazo[1,2-a]pyridine dihydrochloride (36 mg, 0.16 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (34 mg, 0. 18 mmol), and 1-hydroxybenzotriazole (24 mg, 0.18 mmol). The suspension was allowed to stir at r.t. for 17 hr, and the solvent was removed under reduced pressure. The resulting solid was suspended in DMF (1 mL) and stirred for an additional 4 hr before being concentrated under reduced pressure, dissolved in CH2Cl2, filtered through Celite, and chromatographed on silica gel (gradient elution: 0%→20% MeOH in CH2Cl2) to afford the title compound as a yellow solid (22 mg, 35% yield). LC/MS (ESI) retention time: 1.53 min, m/z 683 (MH+); 1H NMR (400 MHz, CDCl3) δ 1.13-1.21 (m, 1 H) 1.29-1.45 (m, 4 H) 1.57-1.67 (m, 1 H) 1.69-1.79 (m,2 H) 1.84-1.95 (m, 1 H) 1.96-2.12 (m, 3 H) 2.30-2.31 (m, 4 H) 2.57-2.75 (m, 2 H) 2.80-2.81 (m, 1 H) 3.60 (s, 4 H) 4.36 (s, 1 H) 4.80 (s, 2 H) 5.06 (s, 1 H) 6.74 (t, J=6.42 Hz, 1 H) 6.79 (s, 1 H) 7.07-7.18 (m, 1 H) 7.32-7.37 (m, 2 H) 7.39-7.46 (m, 2 H) 7.47-7.56 (m, 3 H) 7.60 (s, 1 H) 7.84 (d, J=8.56 Hz, 1 H) 7.99-8.10 (m, 2 H).

후처리

  1. customthe solvent was removed under reduced pressure
  2. stirringstirred for an additional 4 hr
  3. concentrationbefore being concentrated under reduced pressure
  4. dissolutiondissolved in CH2Cl2
  5. filtrationfiltered through Celite
  6. customchromatographed on silica gel (gradient elution: 0%→20% MeOH in CH2Cl2)

출처 및 근거

ORD 기록
ord-2fb490c2f263413f9f4aadc909814460
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07473688B2

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