2-Bromo-5-iodopyrazine → 2-(5-Bromo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamide

HRID 1879148Notes

Reaction equation

HRID 1879148 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.[Br:18][C:19]1[CH:24]=[N:23][C:22](I)=[CH:21][N:20]=1>O1CCCC1.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:22]2[CH:21]=[N:20][C:19]([Br:18])=[CH:24][N:23]=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

5

Reactant 2

HCID 219312002-Bromo-5-iodopyrazineHCID 579593962-Bromo-4-methyl-thiazole-5-carboxylic acid benzylamide

Product 1

HCID 594895392-(5-Bromo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamideYield 9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 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 (400 mg, 1.28 mmol, 1.0 equiv). The sealed tube was purged with nitrogen and Rieke zinc (4 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-bromo-5-iodo-pyrazine (292 mg, 1.0 mmol, 0.8 equiv), Pd(PPh3)4 (59 mg, 0.05 mmol, 4 mol %) in tetrahydrofuran (3 mL). The reaction mixture was purged with nitrogen for 10 min, then stirred at 160° C. for 20 hr. After cooling, the solvent was removed in vacuo and the crude product was purified by preparative HPLC (acetonitrile/water, 0.1% trifluoroacetic acid) to afford 2-(5-bromo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid benzylamide (35 mg, 7%). 1H NMR (400 MHz, CD2Cl2) δ 9.12 (s, 1H), 8.63 (s, 1H), 7.28-7.36 (m, 5H), 6.22 (bs, 1H), 4.59 (d, J=8.0 Hz, 2H), 2.72 (s, 3H); HRMS (M+H)+=389.01.

Workup

  1. customAn oven-dried sealed tube
  2. customThe sealed tube was purged with nitrogen and Rieke zinc (4 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 20 hr
  7. temperatureAfter cooling
  8. customthe solvent was removed in vacuo
  9. customthe crude product was purified by preparative HPLC (acetonitrile/water, 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-b5a9d86cb67548b6937afbc00865249d
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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