3-Bromo-1,1,1-trifluoro-2-propanone → AZD7118 Bromo Trifluoromethyl

HRID 1047142Notes

Reaction equation

[Br:1][C:2]1[C:3]([C:14](=[S:16])[NH2:15])=[CH:4][C:5]([NH:8][C:9]([NH:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=1.Br[CH2:18][C:19](=[O:24])[C:20]([F:23])([F:22])[F:21]>C(#N)C>[Br:1][C:2]1[C:3]([C:14]2[S:16][CH2:18][C:19]([OH:24])([C:20]([F:23])([F:22])[F:21])[N:15]=2)=[CH:4][C:5]([NH:8][C:9]([NH:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A suspension of 5-bromo-2-(3-ethylureido)pyridine-4-carbothioamide (Intermediate 6, 160 g, 510 mmol), 3-bromo-1,1,1-trifluoroacetone (200 g, 1.02 mol) in acetonitrile (3 L) was heated at 80° C. for 20 h. The solution was then cooled down and concentrated. 2:1 Acetonitrile: methyl tert-butyl ether (2.4 L) was added, and the solution thus obtained was placed on a rotovap, and the volume of solvent was reduced by half. The precipitate that formed was filtered and dried in a vacuum oven at 40° C. After letting the filtrate sit, more solid precipitated out and an additional two crops of precipitate were collected and dried in the vacuum oven at 40° C. resulting in a combined collection of 202.4 g (92%) of 1-(5-bromo-4-(4-hydroxy-4-(trifluoromethyl)-4,5-dihydrothiazol-2-yl)pyridin-2-yl)-3-ethylurea as pale yellow solid.

Workup

temperatureThe solution was then cooled down
concentrationconcentrated
addition2:1 Acetonitrile: methyl tert-butyl ether (2.4 L) was added
customthe solution thus obtained
customThe precipitate that formed
filtrationwas filtered
customdried in a vacuum oven at 40° C
custommore solid precipitated out
customan additional two crops of precipitate were collected
customdried in the vacuum oven at 40° C.

Sources & evidence

ORD record: ord-0ac27574699b422c924a45cddcb78efe
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569484B2

Reaction notes

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