Dichloromethane → [(R)-1-(4-{[5-tert-butoxycarbonylamino-2-(2-trifluoromethyl-phenyl)-thiazole-4-carbonyl]-amino}-2-methyl-2H-pyrazol-3-yl)-perhydro-azepin-4-yl]-carbamic acid benzyl ester

In a microwave vial was placed ((R)-1-{4-[(2-bromo-5-tert-butoxycarbonylamino-thiazole-4-carbonyl)-amino]-2-methyl-2H-pyrazol-3-yl}-perhydro-azepin-4-yl)-carbamic acid benzyl ester (132.7 mg, 0.205 mmol), 4,4,5,5-tetramethyl-2-(2-trifluoromethyl-phenyl)-1,3,2-dioxaborolane (278.3 mg, 1.02 mmol, 5.0 eq.), sodium carbonate (65.0 mg, 0.61 mmol, 3.0 eq.), potassium acetate (60.2 mg, 0.61 mmol, 3.0 eq.), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complexed with dichloromethane (1:1) (33.4 mg, 0.041, mmol, 0.20 eq), ACN (10 mL), and water (2.5 mL). The reaction mixture was degassed with N2 for 10 minutes and then subjected to microwave irradiation at 100° C. for 40 minutes. The reaction mixture was diluted with ethyl acetate (50 mL) and then filtered through a pad of Celite. The filtrate was washed with 50% brine/water, water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified via flash column chromatography eluted with 50 to 100% ethyl acetate/heptane to give 83.9 mg (57.4%) of desired product as a foam. MS (ESI) m/z: 714.4 [M+H]+.

1. customThe reaction mixture was degassed with N2 for 10 minutes
2. customirradiation at 100° C. for 40 minutes
3. additionThe reaction mixture was diluted with ethyl acetate (50 mL)
4. filtrationfiltered through a pad of Celite
5. washThe filtrate was washed with 50% brine/water, water and brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe crude was purified via flash column chromatography
10. washeluted with 50 to 100% ethyl acetate/heptane

ORD-Eintrag

ord-a83ce1db9989432e98f095742119aa83

Quelldatensatz

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08669361B2