Dimethyl Sulfoxide → (7aR)-2-Chloro-3-methyl-4-(7a-methyl-3,7-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)benzonitrile

To a 2 M CH2Cl2 solution of oxalyl chloride (68 □L, 0.13 mmol) in CH2Cl2 (2 mL) at −78° C. was added DMSO (17□L, 0.25 mmol). After 20 min, a solution of (7R,7aR)-2-chloro-4-(7-hydroxy-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile (58F) (17 mg, 0.06 mmol) in CH2Cl2 (1 mL) was added. After an additional 20 min at −78° C., triethylamine (62 □L, 0.47 mmol) was added, the cold bath was removed, and the reaction mixture was stirred for 20 min. Water was added and the layers were separated. The organic layer was washed with brine then dried (MgSO4), filtered and concentrated. The resulting residue was purified via preparative HPLC (YMC ODS C-18, 100×20 mm, eluting with 30-80% solvent B (A=90% H2O—10% CH3CN—0.1% TFA and B=10% H2O—90% CH3CN—0.1% TFA) over 15 min; Flow rate at 20 mL/min; UV detection at 220 nm) to provide the title compound (6.3 mg) as a white solid. LC/MS m/z 629 [2M+23]+.

1. waitAfter an additional 20 min at −78° C.
2. customthe cold bath was removed
3. additionWater was added
4. customthe layers were separated
5. washThe organic layer was washed with brine
6. dry with materialthen dried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe resulting residue was purified via preparative HPLC (YMC ODS C-18, 100×20 mm
10. washeluting with 30-80% solvent B (A=90% H2O—10% CH3CN—0.1% TFA and B=10% H2O—90% CH3CN—0.1% TFA) over 15 min

ORD record

ord-67f91e7f6d5844d99c569de4c3c82458

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07405234B2