Methanol → HCID 23654006, compound

HRID 597945Notes

Reaction equation

HRID 597945 reaction equation
[Cl: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[Cl:22].C([O-])([O-])=O.[K+].[K+].CO>O>[Cl: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[Cl:22]

Participants

5

Reactant 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 23654378HCID 23654378, compound

Product 1

HCID 23654006HCID 23654006, compoundYield 90.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
57.5 °C

Procedure

To a solution of CuCl2 (87 mg, 0.65 mmol) and nBuNO2 (950 μl, 0.81 mmol) in MeCN (18 ml) was added a solution of 4-chloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (182 mg, 0.54 mmol) in MeCN (9 ml) at room temperature. After heating the mixture at 50° C. for 4 h, it 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 provide 62 mg (32%) of 3,4-dichloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 4.30 (0.5H), 4.00 (0.5H), 3.92 (3H), 3.83 (1H), 3.74 (1H), 3.38 (1H), 3.25 (2H), 3.10 (1H), 1.16 (3H) ppm. A mixture of 3,4-dichloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (61 mg, 0.17 mmol), K2CO3 (70 mg, 0.51 mmol), MeOH (2.4 ml) and H2O (0.5 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 40 mg (90%) of 3,4-dichloro-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 3.91 (s, 3H), 3.55 (m, 1H), 3.20 (m, 2H), 3.10 (dd, 1H), 2.93 (m, 2H), 2.71 (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-ee9a57e1a0ca4b628dcc13927e3ce266
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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