Dimethylacetamide → 2-{6-[(4-Fluoro-benzyl)-methyl-amino]-pyrazin-2-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide

HRID 1879156Notes

Reaction equation

HRID 1879156 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:14][C:13]([C:15]3[CH:20]=[N:19][CH:18]=[C:17](I)[N:16]=3)=[N:12][C:11]=2[CH3:22])=[O:9])=[CH:4][CH:3]=1.[F:25][C:26]1[CH:34]=[CH:33][C:29]([CH2:30][NH:31][CH3:32])=[CH:28][CH:27]=1.C(N(C(C)C)CC)(C)C.CC(N(C)C)=O>ClCCl>[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:14][C:13]([C:15]3[CH:20]=[N:19][CH:18]=[C:17]([N:31]([CH2:30][C:29]4[CH:33]=[CH:34][C:26]([F:25])=[CH:27][CH:28]=4)[CH3:32])[N:16]=3)=[N:12][C:11]=2[CH3:22])=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 31374DimethylacetamideHCID 81531DiisopropylethylamineHCID 7368601-(4-fluorophenyl)-N-methylmethanamineHCID 866455582-(6-Iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro benzylamide

Product 1

HCID 594895342-{6-[(4-Fluoro-benzyl)-methyl-amino]-pyrazin-2-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamideYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Part C. To a sealed tube was added 2-(6-iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (100 mg, 0.22 mmol, 1.0 equiv), 4-fluoro-N-methyl-benzylamine (58 μL, 0.44 mmol, 2.0 equiv), diisopropylethylamine (17 μL, 0.44 mmol, 2.0 equiv) and dimethyl acetamide (1 mL). The reaction mixture was stirred at 100° C. After 5 hr, the reaction mixture was cooled to room temperature and diluted with dichloromethane, washed with water, brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography [SiO2, ethyl acetate/heptane, 10:90 to 70:30, v/v] and recrystallization from ether/pentane to afford 2-{6-[(4-fluoro-benzyl)-methyl-amino]-pyrazin-2-yl}-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (45 mg, 44%). 1H NMR (400 MHz, CD2Cl2) δ 8.57 (s, 1H), 8.06 (s, 1H), 7.24-7.34 (m, 4H), 6.98-7.05 (m, 4H), 6.18 (bs, 1H), 4.80 (s, 2H), 4.54 (d, J=8.0 Hz, 2H), 3.13 (s, 3H), 2.70 (s, 3H); HRMS (M+H)+=466.15.

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. washwashed with water, brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography [SiO2, ethyl acetate/heptane, 10:90 to 70:30, v/v] and recrystallization from ether/pentane

Sources & evidence

ORD record
ord-a2580e42d8d24b48ad0214a7cfa855ce
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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