N-bromobutanimide → 4-bromo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine

HRID 597936노트

반응식

HRID 597936 반응식
C1C(=O)N([Br:8])C(=O)C1.[CH3:9][O:10][C:11]1[C:12]([NH2:29])=[CH:13][C:14]2[CH:20]([CH3:21])[CH2:19][N:18]([C:22](=[O:27])[C:23]([F:26])([F:25])[F:24])[CH2:17][CH2:16][C:15]=2[N:28]=1>C(Cl)Cl>[Br:8][C:13]1[C:14]2[CH:20]([CH3:21])[CH2:19][N:18]([C:22](=[O:27])[C:23]([F:26])([F:24])[F:25])[CH2:17][CH2:16][C:15]=2[N:28]=[C:11]([O:10][CH3:9])[C:12]=1[NH2:29]

참가 물질

4

반응물 2

HCID 67184N-bromobutanimideHCID 23654286HCID 23654286, 화합물

생성물 1

HCID 236542884-bromo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine수율 37%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

A solution of NBS (1.16 g, 6.50 mmol) in DCM (40 ml) was added dropwise to a stirred and cooled (0-5° C.) solution of 2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (1.97 g, 6.50 mmol) in DCM (40 ml) over a period of 20 min. After 30 minutes of stirring, the reaction was quenched with sat. aq. NaHCO3 and extracted with DCM. The organic layer was dried, concentrated in vacuo and purified by column chromatography to provide 920 mg (37%) of 4-bromo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine. 1H-NMR (CDCl3) δ 4.36 (0.5H), 4.18 (2H), 4.00 (0.5H), 3.95 (3H), 3.79 (1H), 3.74 (1H), 3.70 (1H), 3.38 (1H), 3.23 (1H), 3.07 (1H), 1.19 (3H) ppm. 4-Bromo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (57.0 mg, 0.15 mmol) of was deprotected using K2CO3 (62 mg, 0.45 mmol), MeOH (2.3 ml) and H2O (0.5 ml) at 55-60° C. for 30 minutes. After carefully removing MeOH under reduced pressure, the mixture was diluted with aq. NaHCO3 and extracted with DCM. The organic layer was dried over Na2SO4 and concentrated in vacuo to give 37.0 mg (86%) of 4-bromo-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine. 1H-NMR (CDCl3) δ 3.96 (s, 3H), 3.54 (m, 1H), 3.26 (dd, 2H), 3.18 (dd, 1H), 3.02 (d, 1H), 2.94 (dd, 1H), 2.78 (dd, 1H), 1.32 (d, 3H) ppm.

후처리

  1. stirringAfter 30 minutes of stirring
  2. customthe reaction was quenched with sat. aq. NaHCO3
  3. extractionextracted with DCM
  4. customThe organic layer was dried
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography

출처 및 근거

ORD 기록
ord-d2acb91b9a754f9289ab2139e653caf4
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07897595B2

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