Methyl 6-iodo-5-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrazine-2-carboxylate → Methyl 6-[1-(4-chlorophenyl)-pyrazol-5-yl]-5-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrazine-2-carboxylate

HRID 1259321Notes

Reaction equation

HRID 1259321 reaction equation
I[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5](=[O:12])[N:4]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:3]=1[CH3:23].[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[C:35]([Sn](CCCC)(CCCC)CCCC)=[CH:34][CH:33]=[N:32]2)=[CH:27][CH:26]=1>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.C1COCC1>[Cl:24][C:25]1[CH:26]=[CH:27][C:28]([N:31]2[C:35]([C:2]3[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5](=[O:12])[N:4]([C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=4)[C:3]=3[CH3:23])=[CH:34][CH:33]=[N:32]2)=[CH:29][CH:30]=1

Participants

5

Reactant 2

HCID 66738777Methyl 6-iodo-5-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrazine-2-carboxylateHCID 673457041-(4-chlorophenyl)-5-tributylstannyl-1H-pyrazole

Product 1

HCID 68731759Methyl 6-[1-(4-chlorophenyl)-pyrazol-5-yl]-5-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrazine-2-carboxylateYield 62%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 6-iodo-5-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrazine-2-carboxylate (SM1, 0.133 g, 0.304 mmol), 1-(4-chlorophenyl)-5-tributylstannyl-1H-pyrazole (0.16 g, 0.33 mmol), bis(triphenylphosphine)palladium(II) chloride (0.011 g, 0.015 mmol) and anhydrous THF (1.5 mL) in a vial were heated three consecutive times (for 55 minutes in total) in a microwave reactor (Biotage) at 130° C. until most of the iodo SM was consumed. The dark solution was concentrated to dryness with silica and applied to a silica column. Flash chromatography with ethyl acetate/n-heptane (1:4 through 2:1) gave methyl 6-[2-(4-chlorophenyl)pyrazol-3-yl]-5-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrazine-2-carboxylate (0.0915 g, 62%) as an off-white solid.

Workup

  1. customwas consumed
  2. concentrationThe dark solution was concentrated to dryness with silica

Sources & evidence

ORD record
ord-98055a54d6b24ec391b22cb518a22a91
Source dataset
uspto-grants-2013_06
Patent number
US08466284B2

Reaction notes

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