Methanol → 4-bromo-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine

HRID 597937노트

반응식

HRID 597937 반응식
[Br:1][C:2]1[C:12]2[CH:11]([CH3:13])[CH2:10][N:9](C(=O)C(F)(F)F)[CH2:8][CH2:7][C:6]=2[N:5]=[C:4]([O:20][CH3:21])[C:3]=1[NH2:22].C([O-])([O-])=O.[K+].[K+].CO.O>C([O-])(O)=O.[Na+]>[Br:1][C:2]1[C:12]2[CH:11]([CH3:13])[CH2:10][NH:9][CH2:8][CH2:7][C:6]=2[N:5]=[C:4]([O:20][CH3:21])[C:3]=1[NH2:22]

참가 물질

6

반응물 4

HCID 887Methanol2회HCID 962WaterHCID 11430Potassium CarbonateHCID 236542884-bromo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine

생성물 1

HCID 236539094-bromo-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine수율 86.2%

시약·촉매·용매 1

HCID 516892Sodium Bicarbonate용매

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. customat 55-60° C.
  2. customfor 30 minutes
  3. extractionextracted with DCM
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-8f7773ededab41c48adadef61de594f6
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07897595B2

반응 노트

불러오는 중…