2-Fluoro-3-(tributylstannyl)pyrazine → 4-(3-Fluoropyrazin-2-yl)-2-methyl-6-(methylthio)pyrimidine

HRID 1621508Notes

Reaction equation

I[C:2]1[CH:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([CH3:10])[N:3]=1.[F:11][C:12]1[C:17]([Sn](CCCC)(CCCC)CCCC)=[N:16][CH:15]=[CH:14][N:13]=1>C1(C)C=CC=CC=1.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>[F:11][C:12]1[C:17]([C:2]2[CH:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([CH3:10])[N:3]=2)=[N:16][CH:15]=[CH:14][N:13]=1

Participants

Conditions

Temperature: 140 °C

Procedure

A glass microwave reaction vessel was charged with 4-iodo-2-methyl-6-(methylthio)pyrimidine (266 mg, 1.000 mmol), 2-fluoro-3-(tributylstannyl)pyrazine (387 mg, 1.000 mmol) and tetrakis(triphenylphosphine)palladium(0) (116 mg, 0.100 mmol) in toluene (3 mL). The reaction mixture was stirred and heated in an Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 140° C. for 40 min. The solvent was removed in vacuo and the residue was purified by silica gel chromatography eluting with 40% EtOAc/hexanes to give 4-(3-fluoropyrazin-2-yl)-2-methyl-6-(methylthio)pyrimidine (28 mg, 0.119 mmol, 12% yield). 1H NMR (300 MHz, CDCl3) δ 8.68 (s, 1H); 8.32 (s, 1H); 7.67 (s, 1H); 2.79 (s, 3H); 2.63 (s, 3H). m/z (ESI, +ve ion) 237.1 (M+H)+.

Workup

customA glass microwave reaction vessel
customThe solvent was removed in vacuo
customthe residue was purified by silica gel chromatography
washeluting with 40% EtOAc/hexanes

Sources & evidence

ORD record: ord-fcdad872af894db7afa39ee054092439
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772480B2

Reaction notes

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