Methylamine → HCID 25104409, compound

Tetrahydro-2H-thiopyran-4-one (1.0 g, 8.6 mmol) was dissolved in methanol (40 ml), and methylamine in ethanol (3.3 ml of a 33% solution) was added and the mixture stirred at room temperature for 1 h. The mixture was cooled to −78° C. and a suspension of LiBH4 (0.34 g) in THF (10 ml) was added and stirred for 18 h whilst warming up to room temperature. Water (1 ml) was added and then evaporated and the residue dissolved in chloroform (20 ml). Triethylamine (2 ml) was added and the mixture cooled to 0° C. before adding slowly a solution of [2,1,3]-benzoxadiazole-5-carbonylchloride (1.28 g, 7 mmol) in chloroform (15 ml). The mixture was stirred for 0.5 h and then washed with water (100 ml) and HCl (→pH 2) and NaHCO3 solution (100 ml). The aqueous was extracted with chloroform (100 ml) and the combined organics were dried (MgSO4) and concentrated under vacuum to give a white solid after trituration with diethyl ether (1.6 g). Mp=155-156° C., 1H NMR (300 MHz, CDCl3, rotamers) δ 7.92 (d, J=9.3 Hz, 1H); 7.83 (sb, 1H); 7.40 (d, J=9.3 Hz, 1H); 4.60-4.45 and 3.50-3.30 (m, 1H); 3.10-2.40 (m, 7H) and 2.20-1.85 ppm (s, 4H).

1. temperatureThe mixture was cooled to −78° C.
2. additionwas added
3. stirringstirred for 18 h
4. temperaturewhilst warming up to room temperature
5. customevaporated
6. dissolutionthe residue dissolved in chloroform (20 ml)
7. additionTriethylamine (2 ml) was added
8. temperaturethe mixture cooled to 0° C.
9. stirringThe mixture was stirred for 0.5 h
10. washwashed with water (100 ml) and HCl (→pH 2) and NaHCO3 solution (100 ml)
11. extractionThe aqueous was extracted with chloroform (100 ml)
12. dry with materialthe combined organics were dried (MgSO4)
13. concentrationconcentrated under vacuum
14. customto give a white solid after trituration with diethyl ether (1.6 g)

ORD record

ord-fce7b6b6f84c412f87f6a5d8f47e5577

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642633B2