2,6-Diiodopyrazine → 2-(6-Iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamide

HRID 1879138Notes

Reaction equation

HRID 1879138 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14](Br)=[N:13][C:12]=1[CH3:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I:18][C:19]1[CH:24]=[N:23][CH:22]=[C:21](I)[N:20]=1>O1CCCC1.CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([C:21]2[CH:22]=[N:23][CH:24]=[C:19]([I:18])[N:20]=2)=[N:13][C:12]=1[CH3:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 110020782,6-DiiodopyrazineHCID 579593962-Bromo-4-methyl-thiazole-5-carboxylic acid benzylamide

Product 1

HCID 732132692-(6-Iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamideYield 15.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

Part B. An oven-dried sealed tube was charged with 2-bromo-4-methyl-thiazole-5-carboxylic acid benzylamide (800 mg, 2.57 mmol, 1.0 equiv). The sealed tube was purged with nitrogen and Rieke zinc (10 mL, 10 g of zinc in 100 mL of tetrahydrofuran) was added. The reaction was heated in the microwave oven for 15 min. at 100° C. Stirring was stopped and the remaining zinc was allowed to settle. The supernatant containing the zinc reagent was transferred via syringe to a solution of 2,6-diiodopyrazine (680 mg, 2.1 mmol, 0.8 equiv), Pd(PPh3)4 (236 mg, 0.2 mmol, 7 mol %) in tetrahydrofuran (5 mL) and dimethyl formamide (0.2 mL). The reaction mixture was purged with nitrogen for 10 min, then stirred at 160° C. for 16 hr. After cooling, the solvent was removed in vacuo and the crude product was purified by column chromatography [SiO2, ethyl acetate/heptane, 10:90 to 40:60, v/v] to afford 2-(6-iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamide (140 mg, 13%). MS (M+H)+=436, Rt=1.51 min.

Workup

  1. customAn oven-dried sealed tube
  2. customThe sealed tube was purged with nitrogen and Rieke zinc (10 mL, 10 g of zinc in 100 mL of tetrahydrofuran)
  3. additionwas added
  4. additionThe supernatant containing the zinc reagent
  5. customThe reaction mixture was purged with nitrogen for 10 min
  6. stirringstirred at 160° C. for 16 hr
  7. temperatureAfter cooling
  8. customthe solvent was removed in vacuo
  9. customthe crude product was purified by column chromatography [SiO2, ethyl acetate/heptane, 10:90 to 40:60

Sources & evidence

ORD record
ord-5ec2dc876dd948ea8aceeafdb3ca530b
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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