Water → 2-(6-Benzyl-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamide

HRID 1879139Notes

Reaction equation

HRID 1879139 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+].[CH2:30](B1OC(C)(C)C(C)(C)O1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=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]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=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 38649642-Benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 732132692-(6-Iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamide

Product 1

HCID 249543262-(6-Benzyl-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamideYield 65%

Reagents, catalysts & solvents 2

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

Procedure

Part C. To a solution of 2-(6-iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamide (70 mg, 0.16 mmol, 1.0 equiv) in dimethyl ether (1 mL) was added Na2CO3 (34 mg, 0.32 mmol, 2.0 equiv), benzyl boronic acid pinacol ester (87 μL, 0.40 mmol, 2.5 equiv), PdCl2(dppf) (11 mg, 0.02 mmol, 0.1 equiv) and water (0.1 mL) in a sealed tube. The reaction was immersed in an oil bath preheated to 100° C. After stirring for 4 hr, the reaction 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 give 2-(6-benzyl-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamide (41 mg, 65%). 1H NMR (400 MHz, CD2Cl2) δ 9.17 (s, 1H), 8.47 (s, 1H), 7.22-7.37 (m, 10H), 6.23 (bs, 1H), 4.59 (d, J=8.0 Hz, 2H), 4.19 (s, 2H), 2.72 (s, 3H); HRMS (M+H)+=401.14.

Workup

  1. customThe reaction was immersed in an oil bath
  2. custompreheated to 100° C
  3. temperaturethe reaction 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-5efe5de826d14e409a3dd47886600e4d
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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