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

HRID 597940Notes

Reaction equation

HRID 597940 reaction equation
[CH2:1]([NH:3][C:4]1[C:21]([O:22][CH3:23])=[N:20][C:7]2[CH2:8][CH2:9][N:10]([C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[CH2:11][CH:12]([CH3:13])[C:6]=2[CH:5]=1)[CH3:2].C1C(=O)N([Cl:31])C(=O)C1>CC#N>[Cl:31][C:5]1[C:6]2[CH:12]([CH3:13])[CH2:11][N:10]([C:14](=[O:19])[C:15]([F:17])([F:16])[F:18])[CH2:9][CH2:8][C:7]=2[N:20]=[C:21]([O:22][CH3:23])[C:4]=1[NH:3][CH2:1][CH3:2]

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 23654373N-ethyl-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine

Product 1

HCID 236543744-chloro-N-ethyl-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amineYield 36.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of N-ethyl-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (99.0 mg, 0.30 mmol) in MeCN (5 ml) was added NCS (44.0 mg, 0.33 mmol) at room temperature and the mixture was refluxed for 30 minutes. The reaction was quenched with excess of sat. aq. NaHCO3 and extracted with EtOAc. The organic layer was dried over Na2SO4, concentrated in vacuo and purified by column chromatography to give 40 mg (36%) of 4-chloro-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 4.39 (0.5H), 4.04 (0.5H), 3.94 (3H), 3.83 (1H), 3.78 (1H), 3.72 (1H), 3.45 (1H), 3.35 (2H), 3.25 (1H), 3.09 (1H), 1.19 (6H) ppm. A mixture of 4chloro-N-ethyl-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (37.0 mg, 0.10 mmol), K2CO3 (40 mg), MeOH (1.5 ml) and H2O (0.3 ml) was stirred for 16 h 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 27 mg (93%) of 4-chloro-N-ethyl-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine. 1H-NMR (CDCl3) δ 3.85 (s, 3H), 3.47 (m, 1H), 3.23 (m, 2H), 3.16 (m, 2H), 3.08 (m, 1H), 2.89 (dd, 2H), 2.69 (dd, 1H), 1.22 (d, 3H), 1.09 (t, 3H) ppm.

Workup

  1. temperaturethe mixture was refluxed for 30 minutes
  2. customThe reaction was quenched with excess of sat. aq. NaHCO3
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-0bf695f7f34349cca83873ee0f4be9ff
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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