Methyl iodide → 3-iodo-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine

HRID 597916Notes

Reaction equation

HRID 597916 reaction equation
IC1C(O)=NC2CCN(C(=O)C(F)(F)F)CC(C)C=2C=1.C([O-])([O-])=O.[K+].[K+].CI.[I:29][C:30]1[C:47]([O:48][CH3:49])=[N:46][C:33]2[CH2:34][CH2:35][N:36](C(=O)C(F)(F)F)[CH2:37][CH:38]([CH3:39])[C:32]=2[CH:31]=1>CO.CC(C)=O>[I:29][C:30]1[C:47]([O:48][CH3:49])=[N:46][C:33]2[CH2:34][CH2:35][NH:36][CH2:37][CH:38]([CH3:39])[C:32]=2[CH:31]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 11430Potassium Carbonate2×HCID 236541973-iodo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepineHCID 1784307093-iodo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol

Product 1

HCID 236538093-iodo-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepineYield 30%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 887MethanolSolvent

Procedure

A mixture of 3-iodo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol (100 mg, 250 μmol), K2CO3 (200 mg), MeI (2 ml) and acetone (4 ml) was stirred for 16 h at ambient temperature. The reaction mixture was concentrated in vacuo and purified by column chromatography rendering 25.5 mg (25%) of 3-iodo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine and 41.9 mg (41%) of 3-iodo-1,5-dimethyl-7-(trifluoroacetyl)-1,5,6,7,8,9-hexahydro-2H-pyrido[2,3-d]azepin-2-one. 1H-NMR of O-methylated product (CDCl3) δ 7.79 (2× s, 1H), 3.95 (2× s, 3H), 3.94-3.78 (br m, 2H), 3.59 (br m, 1H), 3.56-3.36 (br m, 1H), 3.22 (m, 1H), 3.08 (br m, 2H), 1.30 (2× d, 3H) ppm. 1H-NMR N-methylated product (CDCl3) δ 7.80 (s, 1H), 3.97-3.65 (br m, 3H), 3.68 (2× s, 3H), 3.44-3.01 (m, 4H), 1.30 (2× d, 3H) ppm. A mixture of 3-iodo-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (25.5 mg, 62.0 μmol), K2CO3 (17.0 mg, 124 μmol) and MeOH (7 ml) was heated for 5 h at 60° C. The reaction mixture was concentrated in vacuo and purified by column chromatography to furnish 5.90 mg (30%) of 3-iodo-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (DMSO-d6) δ 7.84 (s, 1H), 3.83 (s, 3H), 3.00-2.90 (m, 3H), 2.86-2.77 (m, 3H), 2.65 (dd, 1H), 1.21 (d, 3H) ppm.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. custompurified by column chromatography
  3. temperaturewas heated for 5 h at 60° C
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-4c42c4f135fa494ba2b48d7a4315b3d5
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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