Trifluoroacetic acid → HCID 72489373, compound

A suspension of the trifluoroacetic acid salt of 3-Amino-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-b]pyridine-2-yl)-amide (160 mg, 0.39 mmol) in methanol was treated with N,N-diisopropylethylamine (0.28 mL, 1.57 mmol). Stir the reaction at 25° C. for 30 min. The methanol is then removed in vacuo. 4-fluoro-3-(trifluoromethyl)benzaldehyde (0.08 mL, 0.59 mmol) and toluene are then added to the flask and the resulting mixture was stirred at 60° C. for 1 h and was then concentrated in vacuo. This procedure was repeated until the reaction mixture became homogenous when dissolved in toluene. After the final concentration to remove toluene, the reaction mixture was diluted with dichloroethane (15 mL) and then was treated with acetic acid (94 mg) and sodium triacetoxyborohydride (250 mg, 1.18 mmol). The resulting reaction mixture was allowed to stir at 25° C. overnight. At this time, the reaction mixture was poured into 1N NaOH and extracted into methylene chloride. The organics were washed with a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 98:2 methylene chloride/methanol) afforded a colorless oil. The oil was dissolved in diethyl ether and then was concentrated in vacuo to afford 3-(4-Fluoro-3-trifluoromethyl-benzylamino)-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-b]pyridin-2-yl)-amide (19 mg, 25%) as a white solid. LRMS for C20H19F4N5O2S (M+H)30 at m/z=469. The NMR spectrum obtained on the sample is compatible with its structure.

1. customthe reaction at 25° C. for 30 min
2. customThe methanol is then removed in vacuo
3. stirringthe resulting mixture was stirred at 60° C. for 1 h
4. concentrationwas then concentrated in vacuo
5. dissolutiondissolved in toluene
6. concentrationAfter the final concentration
7. customto remove toluene
8. additionthe reaction mixture was diluted with dichloroethane (15 mL)
9. customThe resulting reaction mixture
10. stirringto stir at 25° C. overnight
11. extractionextracted into methylene chloride
12. washThe organics were washed with a saturated aqueous sodium bicarbonate solution
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated in vacuo
16. customFlash chromatography (Merck Silica gel 60, 230-400 mesh, 98:2 methylene chloride/methanol) afforded a colorless oil
17. concentrationwas concentrated in vacuo

ORD record

ord-d7ca95ee217043289d0c97c7835bd7d1

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07947692B2