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

HRID 1879173

Reaction equation

HRID 1879173 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[F:11][C:12]1[CH:34]=[CH:33][C:15]([CH2:16][NH:17][C:18]([C:20]2[S:24][C:23]([C:25]3[CH:30]=[N:29][CH:28]=[C:27](I)[N:26]=3)=[N:22][C:21]=2[CH3:32])=[O:19])=[CH:14][CH:13]=1.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O>[F:11][C:12]1[CH:34]=[CH:33][C:15]([CH2:16][NH:17][C:18]([C:20]2[S:24][C:23]([C:25]3[CH:30]=[N:29][CH:28]=[C:27]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[N:26]=3)=[N:22][C:21]=2[CH3:32])=[O:19])=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 866455582-(6-Iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro benzylamide

Product 1

HCID 249557672-(6-Benzyloxy-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamideYield 60%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of benzyl alcohol (25 μL, 0.24 mmol) in dimethyl acetamide (0.5 mL) in the sealed tube was added NaH (10.4 mg, 0.26 mmol). The reaction mixture was stirred at room temperature. After 30 min, a solution of 2-(6-iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (100 mg, 0.22 mmol) and diisopropyl ethylamine (96 μL, 0.55 mmol) was added to the reaction mixture. The reaction mixture was stirred at 100° C. After 12 hr, the reaction mixture was cooled to room temperature, quenched with methanol, diluted with CH2Cl2, washed with water and brine, then dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography to give the title compound in 60% yield. 1H NMR (400 MHz, CD2Cl2) δ 8.92 (s, 1H), 8.29 (s, 1H), 7.47-7.51 (m, 2H), 7.31-7.40 (m, 5H), 7.02-7.08 (m, 2H), 6.20 (bs, 1H), 5.44 (s, 2H), 4.57 (d, J=8.0 Hz, 2H), 2.72 (s; 3H); MS (ES+) m/z 435.2 (M+1), Rt=1.65 min.

Workup

  1. stirringThe reaction mixture was stirred at 100° C
  2. waitAfter 12 hr
  3. temperaturethe reaction mixture was cooled to room temperature
  4. customquenched with methanol
  5. additiondiluted with CH2Cl2
  6. washwashed with water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-a26e864be7b140e2b5392469d39a8bea
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Linked notes

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