Phosphorus oxychloride → HCID 23653814, compound

Temperature

100 °C

TFAA (2.5 ml) and Et3N (20 ml) was added to a solution of 3-bromo-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol (426 mg, 1.66 mmol) in DCM (60 ml). The mixture was stirred for 1 h at ambient temperature, concentrated in vacuo and parted between NaHCO3 and EtOAc. The organic phase was dried, concentrated and purified by column chromatography to yield 629 mg (93%) of 3-bromo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol. MS (ESI) m/z 353.2/355.1. A mixture of 3-bromo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol (629 mg, 1.78 mmol), DMF (1 ml) and POCl3 (10 ml) was heated at 100° C. for 13 h. The reaction mixture was concentrated in vacuo and purified by column chromatography rendering 185 mg (28%) of 3-bromo-2-chloro-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 7.72 (s, 1H), 4.30-3.05 (m, 7H), 1.38 (d, 1.2H), 1.35 (d, 1.8H). A mixture of 3-bromo-2-chloro-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (79.0 mg, 213 μmol), N2H4H2O (91.0 μl, 1.47 mmol) and EtOH (30 ml) was stirred for 16 h at room temperature. The reaction mixture was parted between EtOAc and sat. aq. NaHCO3. The organic phase was dried over Na2SO4 and concentrated in vacuo. Chromatographic purification rendered 45.0 mg (76%) of 3-bromo-2-chloro-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 7.64 (s, 1H), 3.16 (m, 2H), 3.05 (m, 3H), 2.92 (m, 1H), 2.72 (dd, 1H), 1.33 (d, 3H) ppm.

1. concentrationThe reaction mixture was concentrated in vacuo
2. custompurified by column chromatography
3. dry with materialThe organic phase was dried over Na2SO4
4. concentrationconcentrated in vacuo
5. customChromatographic purification

ORD record

ord-0db55c054cb54d82911da93c462ee76b

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07897595B2