Diisopropylethylamine → methyl [6-(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate

HRID 473887노트

반응식

HRID 473887 반응식
[F:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9](Cl)=[O:10])[CH2:5][CH2:4]1.Cl.[O:13]1[C:19]2[CH:20]=[CH:21][C:22]([C:24]3[CH:25]=[C:26]4[NH:32][C:31]([NH:33][C:34](=[O:37])[O:35][CH3:36])=[N:30][C:27]4=[N:28][CH:29]=3)=[CH:23][C:18]=2[CH2:17][NH:16][CH2:15][CH2:14]1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C=O>[F:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([N:16]2[CH2:17][C:18]3[CH:23]=[C:22]([C:24]4[CH:25]=[C:26]5[NH:32][C:31]([NH:33][C:34](=[O:37])[O:35][CH3:36])=[N:30][C:27]5=[N:28][CH:29]=4)[CH:21]=[CH:20][C:19]=3[O:13][CH2:14][CH2:15]2)=[O:10])[CH2:5][CH2:4]1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 86647862methyl [6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate hydrochlorideHCID 866720264-(Fluoromethyl)piperidine-1-carbonyl chloride

생성물 1

HCID 49833673methyl [6-(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate수율 48%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

A mixture of 4-(fluoromethyl)piperidine-1-carbonyl chloride (reagent preparation 37) (24 mg, 0.13 mmol), methyl [6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate hydrochloride (34 mg, 0.091 mmol), and diisoproylethylamine (59 mg, 0.45 mmol) in dichloromethane (0.5 mL) and N,N-dimethylformamide (0.5 mL) was stirred at room temperature for one hour. The reaction mixture was concentrated then dissolved in methanol (2 mL) and purified directly by preparative reverse phase HPLC to give methyl [6-(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate, (21 mg, 48% yield), (400 MHz, DMSO-d6): 8.41 (br, 1H), 7.87 (s, 1H), 7.54 to 7.44 (m, 2H), 7.05 (d, 1H), 4.45 (s, 2H), 4.31 (dd, 2H), 4.19 (m, 2H), 3.67 to 3.55 (m, 4H), 2.74 (t, 2H), 1.84 (br, 1H), 1.67 to 1.58 (m, 2H), 1.29 to 1.18 (m, 2H); MS (EI) for C24H27FN6O4: 483 (MH+).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthen dissolved in methanol (2 mL)
  3. custompurified directly by preparative reverse phase HPLC

출처 및 근거

ORD 기록
ord-c8da5f3da6814b59afcd00e8584206ea
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637499B2

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