Water → HCID 24954329, compound

HRID 1879146Notes

Reaction equation

HRID 1879146 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([C:16]2[CH:21]=[N:20][CH:19]=[C:18](I)[N:17]=2)=[N:13][C:12]=1[CH3:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[F:30][C:31]([F:44])([F:43])[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]>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([C:16]2[CH:21]=[N:20][CH:19]=[C:18](/[CH:39]=[CH:38]/[C:35]3[CH:34]=[CH:33][C:32]([C:31]([F:30])([F:43])[F:44])=[CH:37][CH:36]=3)[N:17]=2)=[N:13][C:12]=1[CH3:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 6153620trans-2-[4-(Trifluoromethyl)phenyl]vinylboronic acidHCID 732132692-(6-Iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamide

Product 1

HCID 24954329HCID 24954329, compoundYield 70%

Reagents, catalysts & solvents 2

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

Procedure

To a solution of 2-(6-iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamide (100 mg, 0.23 mmol, 1.0 equiv) in dimethyl ether (1 mL) was added Na2CO3 (49 mg, 0.46 mmol, 2.0 equiv), trans-2-(4-trifluoromethylphenyl)vinyl boronic acid (123 mg, 0.57 mmol, 2.5 equiv.), PdCl2(dppf) (17 mg, 0.02 mmol, 0.1 equiv) and water (0.1 mL) in a sealed tube. The reaction vessel was immersed in an oil bath preheated to 100° C. After stirring for 2 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] and recrystallization (methanol/pentane) to afford 4-methyl-2-{6-[(E)-2-(4-trifluoromethyl-phenyl)-vinyl]-pyrazin-2-yl}-thiazole-5-carboxylic acid benzylamide (77 mg, 70%). 1H NMR (400 MHz, CD2Cl2) δ 9.23 (s, 1H), 8.68 (s, 1H), 7.87 (d, J=16.0 Hz, 1H), 7.75 (d, J=8.0 Hz, 2H), 7.66 (d, J=12.0 Hz, 2H), 7.37 (d, J=4.0 Hz, 4H), 7.28-7.36 (m, 1H), 7.28 (d, J=16.0 Hz, 1H), 6.25 (bs, 1H), 4.62 (d, J=4.0 Hz, 2H), 2.74 (s, 3H); HRMS (M+H)+=481.13.

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
  6. customv/v] and recrystallization (methanol/pentane)

Sources & evidence

ORD record
ord-489d59756f9e4d0da94b55381badbe96
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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