2-(Tributylstannyl)pyridine → 2-[2-(6-Fluoro-pyridin-2-yl)-imidazol-1-ylmethyl]-5-methoxy-3-pyridin-2-yl-pyrazine

HRID 1609851Notes

Reaction equation

Cl[C:2]1[C:3]([CH2:10][N:11]2[CH:15]=[CH:14][N:13]=[C:12]2[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[N:17]=2)=[N:4][CH:5]=[C:6]([O:8][CH3:9])[N:7]=1.C([Sn](CCCC)(CCCC)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)CCC>C1(C)C=CC=CC=1.C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:22][C:18]1[N:17]=[C:16]([C:12]2[N:11]([CH2:10][C:3]3[C:2]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)=[N:7][C:6]([O:8][CH3:9])=[CH:5][N:4]=3)[CH:15]=[CH:14][N:13]=2)[CH:21]=[CH:20][CH:19]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 3-chloro-2-[2-(6-fluoro-pyridin-2-yl)-imidazol-1-ylmethyl]-5-methoxy-pyrazine (80 mg, 0.25 mmol), 2-tributylstannylpyridine (138 mg, 0.37 mmol), and PdCl2(PPh3)2 (18 mg, 0.026 mmol) in toluene (10 mL) is heated at 110° C. in a sealed tube for 16 hours. On cooling, the mixture is diluted with DCM (20 mL) and filtered. After the solvent is removed, the residue is purified by PTLC (silica gel; 5% MeOH in DCM) to give 78 mg of 2-[2-(6-fluoro-pyridin-2-yl)-imidazol-1-ylmethyl]-5-methoxy-3-pyridin-2-yl-pyrazine. 1H NMR (CDCl3) 8.59 (d, 1H), 8.15 (d, 1H), 8.08 (s, 1H), 8.02 (d, 1H), 7.85(t, 1H), 7.72 (dd, 1H), 7.32 (dd, 1H), 7.10 (s, 1H), 7.15 (s, 1H), 6.65 (dd, 1H), 6.31 (s, 2H), 4.01 (s, 3H). G. 2-[1-(3-Chloro-5-methoxy-pyrazin-2-ylmethyl)-1H-imidazol-2-yl]-pyrimidine (Compound 8) 1. Synthesis of 2-(1H-imidazol-2-yl)-pyrimidine hydrochloride

Workup

temperatureOn cooling
filtrationfiltered
customAfter the solvent is removed
customthe residue is purified by PTLC (silica gel; 5% MeOH in DCM)

Sources & evidence

ORD record: ord-9668b3f8307146f88657053296baad92
Source dataset: uspto-grants-2006_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06982268B2

Reaction notes

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