Methanol → HCID 23653912, compound

HRID 597942Notes

Reaction equation

HRID 597942 reaction equation
[Br:1][C:2]1[C:19]([O:20][CH3:21])=[N:18][C:5]2[CH2:6][CH2:7][N:8](C(=O)C(F)(F)F)[CH2:9][CH:10]([CH3:11])[C:4]=2[C:3]=1[Br:22].C([O-])([O-])=O.[K+].[K+].CO>O>[Br:1][C:2]1[C:19]([O:20][CH3:21])=[N:18][C:5]2[CH2:6][CH2:7][NH:8][CH2:9][CH:10]([CH3:11])[C:4]=2[C:3]=1[Br:22]

Participants

5

Reactant 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 23654375HCID 23654375, compound

Product 1

HCID 23653912HCID 23653912, compoundYield 92.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
57.5 °C

Procedure

To a solution of CuBr2 (0.64 g, 2.88 mmol) and nBuNO2 (0.42 ml, 3.6 mmol) in MeCN (14 ml) was added a solution of 4-bromo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (0.92 g, 2.41 mmol) in MeCN (10 ml) at room temperature. The reaction mixture was then stirred at 50° C. for 4 h. After removal of MeCN under reduced pressure, the reaction was quenched with sat. aq. NaHCO3 and extracted with EtOAc. The organic layer was dried over Na2SO4, concentrated in vacuo and purified by column chromatography to give 813 mg (76%) of 3,4-dibromo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 4.31 (0.5H), 4.01 (0.5H), 3.91 (3H), 3.85 (1H), 3.69 (1H), 3.39 (1H), 3.23 (1H), 3.12 (1H), 3.06 (1H), 1.17 (3H) ppm. A mixture of 3,4-dibromo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (803 mg, 1.80 mmol), K2CO3 (746 mg, 5.40 mmol), MeOH (32 ml) and H2O (6 ml) was heated at 55-60° C. for 30 minutes. After removal of solvent under reduced pressure, the mixture was taken into aq. NaHCO3 and extracted with DCM. The organic layer was dried and concentrated in vacuo to give 580 mg (92%) of 3,4-dibromo-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 3.89 (s, 3H), 3.63 (m, 1H), 3.21 (m, 2H), 3.09 (dd, 1H), 2.94 (m, 2H), 2.72 (dd, 1H), 1.25 (d, 3H) ppm.

Workup

  1. customAfter removal of solvent under reduced pressure
  2. extractionextracted with DCM
  3. customThe organic layer was dried
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9acbf17809514977beb38de28c9bd550
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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