Water → 4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrimidin-4-yl)thiazol-2-amine

HRID 444889Notes

Reaction equation

[OH-].[Na+].CN(C)/[CH:5]=[CH:6]/[C:7]([C:9]1[S:13][C:12]([N:14]=CN(C)C)=[N:11][C:10]=1[CH3:19])=O.Cl.[F:22][C:23]([F:31])([F:30])[C:24]([CH3:29])([CH3:28])[C:25]([NH2:27])=[NH:26].O>COCCO>[CH3:19][C:10]1[N:11]=[C:12]([NH2:14])[S:13][C:9]=1[C:7]1[CH:6]=[CH:5][N:27]=[C:25]([C:24]([CH3:29])([CH3:28])[C:23]([F:31])([F:30])[F:22])[N:26]=1

Participants

Conditions

Temperature: 125 °C

Procedure

Powdered sodium hydroxide (0.42 g) is added to a solution of N′-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (0.93 g, prepared as described by S. Wang et al J. Med. Chem. 2004, 47, 1662-1675.) and 3,3,3-trifluoro-2,2-dimethyl-propionamidine hydrochloride (0.54 g) in 2-methoxyethanol (7 ml) and the mixture is heated at 125° C. for 1 hour with stirring. The reaction mixture is cooled, water is added, and the aqueous layer is extracted 4-times with 10% methanol in dichloromethane. The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration. HPLC/MS: retention time 1.47 minutes, M+H 303.1.

Workup

temperatureThe reaction mixture is cooled
extractionthe aqueous layer is extracted 4-times with 10% methanol in dichloromethane
customThe combined organic layers are purified by reversed phase chromatography and sodium bicarbonate
additionis added to the fractions
additioncontaining the title compound
customto give a white precipitate, which
filtrationis collected by filtration

Sources & evidence

ORD record: ord-68d860bf1eff41409f84a6d10ffba62f
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08476268B2

Reaction notes

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