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

HRID 597937Notes

Reaction equation

HRID 597937 reaction equation
[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]

Participants

6

Reactant 4

HCID 887Methanol2×HCID 962WaterHCID 11430Potassium CarbonateHCID 236542884-bromo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine

Product 1

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

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

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. 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

Sources & evidence

ORD record
ord-8f7773ededab41c48adadef61de594f6
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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