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

HRID 597938Notes

Reaction equation

HRID 597938 reaction equation
[CH3:1][O:2][C:3]1[C:4]([NH2:21])=[CH:5][C:6]2[CH:12]([CH3:13])[CH2:11][N:10]([C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[CH2:9][CH2:8][C:7]=2[N:20]=1.[CH:22](=O)[CH3:23]>CCO.[Pd]>[CH2:22]([NH:21][C:4]1[C:3]([O:2][CH3:1])=[N:20][C:7]2[CH2:8][CH2:9][N:10]([C:14](=[O:19])[C:15]([F:18])([F:16])[F:17])[CH2:11][CH:12]([CH3:13])[C:6]=2[CH:5]=1)[CH3:23]

Participants

5

Reactant 2

HCID 177AcetaldehydeHCID 23654286HCID 23654286, compound

Product 1

HCID 23654373N-ethyl-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amineYield 56.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of 2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H -pyrido[2,3-d]azepin-3-amine (455 mg, 1.5 mmol), acetaldehyde (253 μl, 4.50 mmol) and 5% Pd/C (23.0 mg) in EtOH (18 ml) was subjected to H2 (50 psi) for 16 h at room temperature. The reaction mixture was filtered, concentrated under reduced pressure and purified by column chromatography to provide 280 mg (56%) of N-ethyl-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine. 1H NMR (CDCl3) δ 6.47 (1H), 4.03 (0.5H), 3.88 (5H), 3.71 (0.5H), 3.43 (1H), 3.64 (3H), 2.98 (2H), 1.20 (6H) ppm. A mixture of of N-ethyl-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (331 mg, 1.00 mmol), K2CO3 (415 mg, 3.00 mmol), MeOH (13 ml) and H20 (2.7 ml) was stirred for 16h at room temperature. 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 204 mg (87%) of N-ethyl-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine. 1H-NMR (CDCl3) δ 6.48 (s, 1H), 3.87 (s, 3H), 3.80 (br s, 1H), 3.10-2.70 (m, 9H), 2.48 (br s, 1H), 1.26 (d, 3H), 1.24 (t, 3H) ppm.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated under reduced pressure
  3. custompurified by column chromatography

Sources & evidence

ORD record
ord-c551a14fbf6e4991b10ba142d28e0ae4
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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