Diisopropylethylamine → Gsk 1034702

4-Fluoro-6-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one (12.5 mmol, 3.6 g) (D5a) was dissolved in dichloromethane (50 ml), diisopropylethylamine (3 eq., 37.6 mmol, ˜6.4 ml), and tetrahydro-4H-pyran-4-one (4 eq., 50 mmol, ˜5 g) were added in that order at room temperature; sodium triacetoxyborohydride (3 eq., 37.6 mmol, ˜8 g) was added at room temperature and the mixture was stirred at room temperature for one overnight. The reaction mixture was diluted with dichloromethane (100 ml) and quenched with NaHCO3 (saturated aqueous solution); methanol was added to dissolve the solid which developed in the organic layer; the two phases were separated and the aqueous phase was extracted with dichloromethane (2×); the combined organics were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated to afford 3.8 g, 92%. The material was triturated with diethyl ether and filtered to afford 3.6 g title compound. This was dissolved in MeOH/DCM and 2 eq of HCl (1M in Et2O) were added. The mixture was stirred at room temperature for 10 minutes, solvent was evaporated and the solid was triturated with Et2O to afford another batch, 3.8 g, pale grey solid.

1. customquenched with NaHCO3 (saturated aqueous solution)
2. additionmethanol was added
3. dissolutionto dissolve the solid which
4. customthe two phases were separated
5. extractionthe aqueous phase was extracted with dichloromethane (2×)
6. washthe combined organics were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customthe solvent was evaporated
10. customto afford 3.8 g, 92%
11. customThe material was triturated with diethyl ether
12. filtrationfiltered

ORD record

ord-2393db63babe43d7a8cb8d8279ee4e1a

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481566B2