Hydrochloric Acid → 7-chloro-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine

Temperature

0 °C

7-Chloro-1H-pyrido[2,3-b][1,4]thiazin-2(3H)-one (1.2 g, 5.98 mmol) was suspended in THF (5.0 mL), cooled to 0° C. and treated with BH3-THF (47.8 mL, 47.8 mmol, 1.0M in THF). The reaction was stirred at rt for 30 min and heated at 45° C. for 2 h. At this time more BH3-THF (47.8 mL, 47.8 mmol, 1.0M in THF) was added and the reaction was heated at 45° C. for 16 h. The reaction was then treated with 100 mL of MeOH and it was refluxed for 30 min. After this time the reaction was cooled to rt and acidified to pH 2 with aqueous HCl. The reaction was then basified to pH 14 with aqueous NaOH and the mixture was then extracted with EtOAc (3×80 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. The resulting white solid was triturated with hot EtOAc and the mixture was allowed to cool to rt for 20 min. After filtration, the precipitate was dried over MgSO4 and evaporated in vacuo to give 7-chloro-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.60 (1H, d, J=2.3 Hz), 6.85 (1H, d, J=2.2 Hz), 6.52 (1H, t, J=3.0 Hz), 3.43-3.50 (2H, m), 3.04-3.15 (2H, m). Mass Spectrum (ESI) m/e=187.0 (M+1).

1. temperatureheated at 45° C. for 2 h
2. temperaturethe reaction was heated at 45° C. for 16 h
3. temperaturewas refluxed for 30 min
4. temperatureAfter this time the reaction was cooled to rt
5. extractionthe mixture was then extracted with EtOAc (3×80 mL)
6. dry with materialThe separated organic layer was dried over MgSO4
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe resulting white solid was triturated with hot EtOAc
10. temperatureto cool to rt for 20 min
11. filtrationAfter filtration
12. dry with materialthe precipitate was dried over MgSO4
13. customevaporated in vacuo

ORD record

ord-abbc36c45b59455f9f2359ffd3095d12

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765940B2