4-Methylmorpholine → HCID 71533385, compound

A solution of 3-amino-6-chloro-5-trifluoromethyl-pyridine-2-carboxylic acid (Intermediate 5) (0.143 g, 0.594 mmol) in DMF (5 ml) was treated with HATU (226 mg, 0.594 mmol), 1H-pyrazole-5-amine (74.1 mg, 0.892 mmol) and 4-methylmorpholine (0.118 ml, 1.189 mmol). The mixture was stirred at RT for 30 minutes followed by 80° C. for 2 hours before cooling to RT. The reaction mixture was diluted with 2M NaOH (20 ml) and the product extracted with EtOAc (2×60 ml). The organics were combined, washed with brine (20 ml), dried over MgSO4 and concentrated in vacuo to give a brown oil. This oil was taken up as a solution in DCM (2 ml), and after 5 minutes, a white precipitate was present. This was filtered under vacuum, washed with DCM and dried on high vacuum. The material was taken up in EtOAc (50 ml) and washed successively with 2M NaOH (2×20 ml), brine (10 ml), dried over MgSO4 and concentrated in vacuo to give a yellow solid. This was taken up in MeOH (3 ml) and loaded onto a 10 g SCX-2 cartridge, eluted with MeOH (50 ml), then a solution of 7M NH3 in MeOH (50 ml). The relevant fractions were combined and concentrated in vacuo to afford the title compound.

1. waitfollowed by 80° C. for 2 hours
2. temperaturebefore cooling to RT
3. extractionthe product extracted with EtOAc (2×60 ml)
4. washwashed with brine (20 ml)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo
7. customto give a brown oil
8. waitafter 5 minutes
9. filtrationThis was filtered under vacuum
10. washwashed with DCM
11. customdried on high vacuum
12. washwashed successively with 2M NaOH (2×20 ml), brine (10 ml)
13. dry with materialdried over MgSO4
14. concentrationconcentrated in vacuo
15. customto give a yellow solid
16. washeluted with MeOH (50 ml)
17. concentrationconcentrated in vacuo

ORD record

ord-ade1ba6e341341a288f9d85639e71edc

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056867B2