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

HRID 597936Notes

Reaction equation

HRID 597936 reaction equation
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]

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 23654286HCID 23654286, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-d2acb91b9a754f9289ab2139e653caf4
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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