3-Bromo-1,1,1-trifluoro-2-propanone → HCID 16112837, compound

HRID 1993602Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:27][C:28]([NH2:30])=[S:29])([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.Br[CH2:32][C:33](=O)[C:34]([F:37])([F:36])[F:35]>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:27][C:28]2[S:29][CH:32]=[C:33]([C:34]([F:37])([F:36])[F:35])[N:30]=2)([C:16]2[CH:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To 1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)thiourea (15 mg, 0.033 mmol) in ethanol (1 mL) in a two dram vial was added 3-bromo-1,1,1-trifluoropropan-2-one (6.3 mg, 0.033 mmol). The vial was heated in a shaker at 80° C. for 2 hours. The reaction was concentrated and crude mixture was purified by silica gel ISCO chromatography (4 g column) using hexanes/EtOAc (0-25% over 20 min) to give the N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-4-(trifluoromethyl)thiazol-2-amine as a white foam (11 mg, 61% yield). LCMS: 4.3 min [M+1] 456.1 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CDCl3) δ ppm 3.58 (d, J=13.21 Hz, 1H), 4.60 (d, J=12.96 Hz, 1H), 6.46 (d, J=7.58 Hz, 2H), 6.88 (s, 1H), 7.05 (t, J=7.46 Hz, 2H), 7.10-7.15 (m, 2H), 7.24-7.29 (m, 2H), 7.35 (d, J=9.78 Hz, 1H), 7.64-7.71 (m, 2H), 8.01 (s, 1H), 8.31 (d, J=2.20 Hz, 1H).

Workup

concentrationThe reaction was concentrated
customcrude mixture was purified by silica gel ISCO chromatography (4 g column)
customhexanes/EtOAc (0-25% over 20 min)

Sources & evidence

ORD record: ord-739a7983e5f84491a078ff9a910fa931
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652023B2

Reaction notes

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