1,4-Dioxane → HCID 58459346, compound

A mixture of (S)-tert-butyl 1-(5,6-difluoro-1-(5-fluoropyridin-3-yl)-1H-benzo[d]-imidazol-2-yl)ethylcarbamate (0.460 g, 1.17 mmol) in hydrochloric acid, 4 M solution in 1,4-dioxane (5.86 mL, 23.45 mmol) was stirred at rt. After 4 h, the mixture was partitioned between DCM (50 mL) and water (50 mL). The aqueous layer was washed with DCM (1×50 mL) to remove an organic impurity. The aqueous layer was treated with satd. aq. sodium bicarbonate solution (50 mL) and extracted with DCM (1×50 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep™ pre-packed silica gel column (40 g), eluting with a gradient of 0% to 50% DCM:MeOH:NH4OH (89:9:1) in DCM, to provide (S)-1-(5,6-difluoro-1-(5-fluoropyridin-3-yl)-1H-benzo[d]imidazol-2-yl)ethanamine as a colorless syrup: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.84 (1H, d, J=2.7 Hz), 8.75 (1H, s), 8.24 (1H, dt, J=9.4, 2.3 Hz), 7.79 (1H, dd, J=11.0, 7.4 Hz), 7.40 (1H, dd, J=10.4, 7.2 Hz), 3.96 (1H, q, J=6.6 Hz), 2.00 (2H, d, J=4.5 Hz), 1.37 (3H, d, J=6.7 Hz); LC-MS (ESI) m/z 293.0 [M+H]+.

1. customthe mixture was partitioned between DCM (50 mL) and water (50 mL)
2. washThe aqueous layer was washed with DCM (1×50 mL)
3. customto remove an organic impurity
4. additionThe aqueous layer was treated with satd
5. extractionaq. sodium bicarbonate solution (50 mL) and extracted with DCM (1×50 mL)
6. dry with materialThe organic layer was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude material was absorbed onto a plug of silica gel
10. custompurified by chromatography through a Redi-Sep™ pre-packed silica gel column (40 g)
11. washeluting with a gradient of 0% to 50% DCM:MeOH:NH4OH (89:9:1) in DCM

ORD record

ord-5412e356c8f94cef856e675449f91abf

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575183B2