5-Chloro-2-(methylsulfanyl)pyrimidine-4-carboxylic acid → (5-Chloro-2-(methylthio)pyrimidin-4-YL)(2-(difluoromethoxy)phenyl)methanol

HRID 518784Notes

Reaction equation

[F:1][CH:2]([F:12])[O:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=[O:7].[Cl:13][C:14]1[C:15](C(O)=O)=[N:16][C:17]([S:20][CH3:21])=[N:18][CH:19]=1>C1(OC)C=CC=CC=1>[Cl:13][C:14]1[C:15]([CH:6]([C:5]2[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=2[O:3][CH:2]([F:12])[F:1])[OH:7])=[N:16][C:17]([S:20][CH3:21])=[N:18][CH:19]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 780 mg of 2-(difluoromethoxy)benzaldehyde and 300 mg of 5-chloro-2-(methylsulfanyl)pyrimidine-4-carboxylic acid 1 in 15 ml of anisole is microwave-heated at 130° C. for 45 min and then again for 15 min and again at 140° C. for 15 min. 160 mg of 5-chloro-2-(methylsulfanyl)pyrimidine-4-carboxylic acid 1 is then added and the mixture is again heated at 130° C. for 30 min. The mixture is concentrated under vacuum and purified on 40 g of silica, elution being carried out with 0-10% of ethyl acetate in heptane, so as to obtain 268 mg of [5-chloro-2-(methylsulfanyl)pyrimidin-4-yl][2-(difluoromethoxy)phenyl]methanol 6 in the form of a colourless oil.

Workup

waitagain at 140° C. for 15 min
temperaturethe mixture is again heated at 130° C. for 30 min
concentrationThe mixture is concentrated under vacuum
custompurified on 40 g of silica, elution

Sources & evidence

ORD record: ord-e0297e234b374aa0a7b1a04d7c1e767e
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115140B2

Reaction notes

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