Potassium Carbonate → 2-(5-Cyclopropylcarbamoyl-2-methyl-phenylamino)-4-(4-fluoro-3-methyl-phenyl)-thiazole-5-carboxylic acid benzylamide

HRID 1993805Notes

Reaction equation

HRID 1993805 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([NH:16][C:17]2[CH:22]=[C:21]([C:23](=[O:28])[NH:24][CH:25]3[CH2:27][CH2:26]3)[CH:20]=[CH:19][C:18]=2[CH3:29])=[N:13][C:12]=1Br)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][C:37]=1[F:38].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([NH:16][C:17]2[CH:22]=[C:21]([C:23](=[O:28])[NH:24][CH:25]3[CH2:27][CH2:26]3)[CH:20]=[CH:19][C:18]=2[CH3:29])=[N:13][C:12]=1[C:34]1[CH:35]=[CH:36][C:37]([F:38])=[C:32]([CH3:31])[CH:33]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2774580(4-Fluoro-3-methylphenyl)boronic acidHCID 111792134-Bromo-2-(5-cyclopropylcarbamoyl-2-methyl-phenylamino)-thiazole-5-carboxylic acid benzylamide

Product 1

HCID 111915312-(5-Cyclopropylcarbamoyl-2-methyl-phenylamino)-4-(4-fluoro-3-methyl-phenyl)-thiazole-5-carboxylic acid benzylamideYield 72.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A microwave reaction flask was charged with 4-bromo-2-(5-cyclopropylcarbamoyl-2-methyl-phenylamino)-thiazole-5-carboxylic acid benzylamide (10 mg, 0.02 mmol, 1.0 eq), 3-methyl-4-fluorophenylboronic acid (32 mg, 0.21 mmol, 10 eq), tetrakistriphenylphosphine palladium (5 mg, 0.004 mmol, 0.2 eq), 200 μL of dioxane, and 200 μL of saturated aqueous K2CO3. The mixture was heated with stirring in the microwave at 120° C. for 10 minutes. The layers were separated and dioxane layer was concentrated and purified by preparative HPLC. Fractions containing product were concentrated to provide the title compound as a white solid (7.5 mg, 71%). HPLC (4 minutes gradient) tR 2.61 min; MS m/z 515.24 [M+H]+; 1H NMR (DMSO-d6, 500 MHz) δ 0.53 (m, 2H), 0.66 (m, 2H), 2.16 (s, 3H), 2.29 (s, 3H), 2.82 (m, 1H), 4.29 (d, J=4.3, 2H), 7.05 (t, J=8.9, 1H), 7.20-7.30 (m, 6H), 7.44-7.51 (m, 3H), 8.30-8.36 (m, 3H), 9.72 (s, 1H) ppm.

Workup

  1. customA microwave reaction flask
  2. temperatureThe mixture was heated
  3. customThe layers were separated
  4. concentrationdioxane layer was concentrated
  5. custompurified by preparative HPLC
  6. additionFractions containing product
  7. concentrationwere concentrated

Sources & evidence

ORD record
ord-082d3e449053401db75bfbd268313dae
Source dataset
uspto-grants-2010_01
Patent number
US07652044B2

Reaction notes

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