Hydrochloric Acid → 4-(4-Bromo-2-chloro-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine

Temperature

4 °C

To a solution of 4-(4-bromo-2-chloro-phenyl)-1-methyl-3-(2-pyridyl)-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one (5.83 g, 13.0 mmol) in THF (50 mL) was added a solution of borane THF complex (40 mL, 1M in THF, 40 mmol, Acros) at rt. Subsequently, the mixture was heated under reflux for about 2 h. After cooling to about 4° C., HCl (5 M aq, 40 mL) was added dropwise and the mixture was stirred for about 18 h at rt, then NaOH (2 M aq, 110 mL) and ethyl acetate (200 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were washed with water (2×50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, ethyl acetate) to give 4-(4-bromo-2-chloro-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (4.86 g, 11.1 mmol, 86%). LC-MS (Table 1, Method a) Rt=4.54 min, m/z 435, 437 (M+H)+

1. temperatureSubsequently, the mixture was heated
2. temperatureunder reflux for about 2 h
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
5. washThe combined organic layers were washed with water (2×50 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by column chromatography (SiO2, ethyl acetate)

ORD record

ord-e92d3e3b11ed4f398ae67b538b98584a

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150592B2