5-(Tributylstannyl)-1,3-thiazole → (S)-4-chloro-N-[1-(4-fluorophenyl)ethyl]-6-(thiazol-5-yl)pyrimidine-2-amine

HRID 2043423Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([NH:9][C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH3:11])[N:3]=1.C([Sn](CCCC)(CCCC)[C:24]1[S:28][CH:27]=[N:26][CH:25]=1)CCC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:6]1[CH:7]=[C:2]([C:24]2[S:28][CH:27]=[N:26][CH:25]=2)[N:3]=[C:4]([NH:9][C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH3:11])[N:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

286 mg of (S)-4,6-dichloro-N-[1-(4-fluorophenyl)ethyl]pyrimidine-2-amine (Reference Example 1), 411 mg of 5-(tributylstannyl)thiazole and 115 mg of tetrakis(triphenylphosphine)palladium were added in turn to degassed dimethylformamide, and then the mixture was stirred at 100° C. for 5 hours under argon atmosphere. The reaction solution was diluted with ethyl acetate. The solution was washed in turn with water and brine and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and then the obtained residue was purified by silica gel column chromatography to obtain 175 mg of (S)-4-chloro-N-[1-(4-fluorophenyl)ethyl]-6-(thiazol-5-yl)pyrimidine-2-amine as a white solid.

Workup

customto degassed dimethylformamide
additionThe reaction solution was diluted with ethyl acetate
washThe solution was washed in turn with water and brine
dry with materialdried over magnesium sulfate
distillationThe solvent was distilled off under reduced pressure
customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-1d16acbe6c334646af8026091c4087f9
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586591B2

Reaction notes

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