Trifluoroacetic acid → HCID 58557354, compound

Temperature

40 °C

To a 250 mL round-bottomed flask 1-((1S,2R,4S)-4-(dibenzylamino)-2-methylcyclopentyl)-2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)ethanone (11.2 g, 17.51 mmol) in acetonitrile (60 ml) was added. The mixture was cooled with an ice bath and TFA (2.70 ml, 35.0 mmol) and TFAA (24.46 ml, 175 mmol) was added. The resulting mixture was warmed and stirred at about 40° C. for about 42 h. The reaction was then cooled in an ice bath and quenched with methanol (7 mL). After warming to ambient temperature and stirring for about 1 h, it was poured into ethyl acetate (100 mL) and aqueous sodium carbonate (10% w/v, 200 mL). The layers were separated and the organic layer concentrated. The residue was dissolved in THF (120 ml) and 2N sodium hydroxide (35.0 ml, 70.0 mmol) was added. The reaction mixture was warmed to about 60° C. and stirred for about 16 h. After cooling to ambient temperature, 2-methyl-tetrahydrofuran (100 mL) and brine (100 mL) were added and the layers separated. The aqueous layer was extracted with 2-methyl-tetrahydrofuran (50 mL) and the combined organic layers washed with brine (50 mL). The organic layer was concentrated, dissolved in EtOH (100 mL) and treated with charcoal (500 mg) for about 1 h. The charcoal was filtered off and the ethanol removed under reduced pressure. The residue was taken up in CHCl3 (50 mL) warmed to about 50° C. and heptane (50 mL) was added. After cooling to ambient temperature, the product was collected, washed with 1:2 CHCl3:heptane (30 mL) and dried in a vacuum oven to afford (1S,3S,4R)-N,N-dibenzyl-3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-4-methylcyclopentanamine as a tan solid (5.1 g, 67%) 1H NMR (400 MHz, DMSO) δ 12.18 (s, 1H), 8.52 (s, 1H), 7.60 (s, 1H), 7.44-7.29 (m, 8H), 7.22 (t, J=7.2 Hz, 2H), 6.84 (d, J=3.4 Hz, 1H), 3.86 (dd, J=17.6, 8.8 Hz, 1H), 3.77-3.59 (m, 4H), 3.41-3.17 (m, 2H), 2.64-2.53 (m, 1H), 2.32-2.06 (m, 3H), 1.49-1.30 (m, 1H), 0.40 (d, J=7.0 Hz, 3H).

1. temperatureThe mixture was cooled with an ice bath
2. temperatureThe resulting mixture was warmed
3. temperatureThe reaction was then cooled in an ice bath
4. customquenched with methanol (7 mL)
5. temperatureAfter warming to ambient temperature
6. stirringstirring for about 1 h
7. additionit was poured into ethyl acetate (100 mL) and aqueous sodium carbonate (10% w/v, 200 mL)
8. customThe layers were separated
9. concentrationthe organic layer concentrated
10. dissolutionThe residue was dissolved in THF (120 ml)
11. temperatureThe reaction mixture was warmed to about 60° C.
12. stirringstirred for about 16 h
13. temperatureAfter cooling to ambient temperature
14. customthe layers separated
15. extractionThe aqueous layer was extracted with 2-methyl-tetrahydrofuran (50 mL)
16. washthe combined organic layers washed with brine (50 mL)
17. concentrationThe organic layer was concentrated
18. dissolutiondissolved in EtOH (100 mL)
19. additiontreated with charcoal (500 mg) for about 1 h
20. filtrationThe charcoal was filtered off
21. customthe ethanol removed under reduced pressure
22. temperaturewarmed to about 50° C.
23. additionheptane (50 mL) was added
24. temperatureAfter cooling to ambient temperature
25. customthe product was collected
26. washwashed with 1:2 CHCl3
27. dry with materialheptane (30 mL) and dried in a vacuum oven

ORD record

ord-526d44add61e4757a41257cc5e0b11eb

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426411B2