Potassium Carbonate → 3-chloro-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine

Temperature

125 °C

A mixture of 2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (100 mg, 347 μmol), PCl5 (722 mg, 3.47 mmol) and POCl3 (10 ml) was heated at 125° C. in a sealed tube for 16 h. The reaction mixture was parted between DCM and sat. aq. NaHCO3. The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo. Chromatographic purification rendered 23.5 mg (21%) of 3-chloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. A mixture of 3-chloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (23.5 mg, 72.8 μmol) and K2CO3 (30 mg) in MeOH (7 ml) was heated at reflux for 2 h. The reaction mixture was concentrated in vacuo and chromatographic purification of the resulting residue rendered 11.2 mg (68%) of 3-chloro-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 7.48 (s, 1H), 3.99 (s, 3H), 3.55-3.30 (m, 4H), 3.25 (m, 1H), 3.07 (m, 1H), 2.85 (dd, 1H), 1.43 (d, 3H) ppm.

1. washThe organic phase was washed with brine
2. dry with materialdried over Na2SO4
3. concentrationconcentrated in vacuo
4. customChromatographic purification
5. temperaturewas heated
6. temperatureat reflux for 2 h
7. concentrationThe reaction mixture was concentrated in vacuo and chromatographic purification of the resulting residue

ORD record

ord-6370fb5488be44dfaa34697a5100097f

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07897595B2