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

HRID 1879155

Reaction equation

HRID 1879155 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:14][C:13](Br)=[N:12][C:11]=2[CH3:16])=[O:9])=[CH:4][CH:3]=1.[I:19][C:20]1[CH:25]=[N:24][CH:23]=[C:22](I)[N:21]=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>[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:14][C:13]([C:22]3[CH:23]=[N:24][CH:25]=[C:20]([I:19])[N:21]=3)=[N:12][C:11]=2[CH3:16])=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 110020782,6-DiiodopyrazineHCID 666314052-Bromo-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

Product 1

HCID 866455582-(6-Iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro benzylamideYield 10.5%

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 4-fluoro-benzylamide (1.0 g, 3.03 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 (704 mg, 2.1 mmol, 0.7 equiv), Pd(PPh3)4 (175 mg, 0.2 mmol, 5 mol %) in tetrahydrofuran (2 mL) and dimethyl formamide (0.1 mL). The reaction mixture was purged with nitrogen for 10 min, then stirred at 140° C. for 20 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 4-fluoro-benzylamide (100 mg, 7%). MS (M+H)+=455.1, Rt=1.53 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 140° C. for 20 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-454485d9a7f54213a5af67761fb45243
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Linked notes

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