Water → HCID 68490041, compound

HRID 1879166Notes

Reaction equation

HRID 1879166 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:14][C:13]([C:15]3[CH:20]=[N:19][CH:18]=[C:17](I)[N:16]=3)=[N:12][C:11]=2[CH3:22])=[O:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[F:31][C:32]1[CH:37]=[CH:36][C:35](/[CH:38]=[CH:39]/B(O)O)=[CH:34][CH:33]=1.O>COC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:14][C:13]([C:15]3[CH:20]=[N:19][CH:18]=[C:17](/[CH:39]=[CH:38]/[C:35]4[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=4)[N:16]=3)=[N:12][C:11]=2[CH3:22])=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 5706776trans-2-(4-Fluorophenyl)vinylboronic acidHCID 866455582-(6-Iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro benzylamide

Product 1

HCID 68490041HCID 68490041, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8254Dimethyl EtherSolvent

Procedure

Part A. To a solution of 2-(6-iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (250 mg, 0.55 mmol, 1.0 equiv) in dimethyl ether (3 mL) was added Na2CO3 (175 mg, 1.65 mmol, 3.0 equiv), trans-2-(4-fluorophenyl)vinyl boronic acid (274 mg, 1.65 mmol, 3.0 equiv), PdCl2(dppf) (40 mg, 0.06 mmol, 0.1 equiv) and water (0.4 mL) in a sealed tube. The reaction vessel was immersed in an oil bath preheated to 100° C. After stirring for 12 hr, the reaction mixture was cooled and the solvent was removed in vacuo. The crude product was purified by column chromatography [SiO2, methanol/dichloromethane, 0:100 to 10:90, v/v] to give 2-{6-[(E)-2-(4-fluoro-phenyl)-vinyl]-pyrazin-2-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (160 mg, 65%). MS (M+H)+=449.1, Rt=1.64 min.

Workup

  1. customThe reaction vessel was immersed in an oil bath
  2. custompreheated to 100° C
  3. temperaturethe reaction mixture was cooled
  4. customthe solvent was removed in vacuo
  5. customThe crude product was purified by column chromatography [SiO2, methanol/dichloromethane, 0:100 to 10:90

Sources & evidence

ORD record
ord-1a9e1cd966ac434a87b792573154a8d1
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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