5-Chloropyrimidine → HCID 178461721, compound

Participants

Reaction Steps

The 5-(3,3-dimethyl-but-1-ynyl)-3-[(3-hydroxy-1-(S)-methyl-propyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid TFA salt (100 mg, 0.239 mmol) and 5-chloro-pyrimidine (137 mg, 1.194 mmol) were dissolved in DMSO (2 mL). To this solution tBuOK (107 mg, 0.956 mmol) was added in one portion at rt. The reaction was allowed to stir at rt for 1 h and then heated to 60° C. for 1.5 h. Additional tBuOK (50 mg) and 5-chloro-pyrimidine (69 mg) were added and the reaction was run at 60° C. for another 1 h. The reaction was then heated to 100° C. for another 1 h. Additional tBuOK (50 mg) and 5-chloro-pyrimidine (69 mg) were added and the reaction was run at 100° C. overnight. The reaction was cooled to rt and quenched with a 20% (v/v) solution of acetic acid in water. The reaction was diluted with MeOH and 5-(3,3-dimethyl-but-1-ynyl)-3-{(trans-4-methyl-cyclohexanecarbonyl)-[1-(S)-methyl-3-(pyrimidin-5-yloxy)-propyl]-amino}-thiophene-2-carboxylic acid (4 mg, 2.7%) was isolated by reverse phase HPLC as the TFA salt.

Provenance & Evidence