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

HRID 1609851
Notes
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Reaction equation

HRID 1609851 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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 2

HCID 6077842-(Tributylstannyl)pyridineHCID 102454163-Chloro-2-[2-(6-fluoro-pyridin-2-yl)-imidazol-1-ylmethyl]-5-methoxy-pyrazine

Product 1

HCID 100671892-[2-(6-Fluoro-pyridin-2-yl)-imidazol-1-ylmethyl]-5-methoxy-3-pyridin-2-yl-pyrazineYield 86.1%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalyst
HCID 1140
Toluene
Solvent
HCID 6344DichloromethaneSolvent

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

  1. temperatureOn cooling
  2. filtrationfiltered
  3. customAfter the solvent is removed
  4. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes