Dimethylformamide → 4-trifluoromethyl-4H-thiazole-2-carboxylic acid-(6-acetyl-3-methoxy-2-methyl-phenyl)-amide

HRID 925919Notes

Reaction equation

HRID 925919 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[N:4]=[C:5]([C:8]([OH:10])=O)[S:6][CH:7]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:24][C:25]1[C:30]([CH3:31])=[C:29]([O:32][CH3:33])[CH:28]=[CH:27][C:26]=1[C:34](=[O:36])[CH3:35]>C(Cl)Cl.O1CCOCC1>[C:34]([C:26]1[C:25]([NH:24][C:8]([C:5]2[S:6][CH2:7][CH:3]([C:2]([F:1])([F:12])[F:11])[N:4]=2)=[O:10])=[C:30]([CH3:31])[C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)(=[O:36])[CH3:35]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 186730104-(Trifluoromethyl)thiazole-2-carboxylic acidHCID 250673162'-Amino-3'-methyl-4'-methoxyacetophenone

Product 1

HCID 667303754-trifluoromethyl-4H-thiazole-2-carboxylic acid-(6-acetyl-3-methoxy-2-methyl-phenyl)-amideYield 86%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 4-(trifluoromethyl)-1,3-thiazole-2-carboxylic acid (3.5 g, 1 eq.) in DCM (35 mL) at 0° C. under nitrogen was added anhydrous DMF (few drops) and oxalyl chloride (3.14 mL, 2 eq.). At the end of the gas evolution, the reaction mixture was allowed to warm up to room temperature. The mixture was stirred at room temperature for 2 hrs and was evaporated. Dioxane (70 mL) was added under nitrogen followed by a solution of 1-(2-amino-4-methoxy-3-methyl-phenyl)-ethanone 9 (3.18 g, 1 eq.) in dioxane (15 mL). The reaction mixture was stirred at room temperature for 16 hrs. The reaction mixture was washed with saturated NaHCO3. Organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was triturated in Et2O to yield compound 202b as a white solid in 86% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 2.15 (s, 3H), 2.58 (s, 3H), 3.94 (s, 3H), 6.82 (d, J=8.55 Hz, 1H), 7.78 (d, J=8.55 Hz, 1H), 8.01 (s, 1H), 11.25 (s, 1H).

Workup

  1. customwas evaporated
  2. additionDioxane (70 mL) was added under nitrogen
  3. stirringThe reaction mixture was stirred at room temperature for 16 hrs
  4. washThe reaction mixture was washed with saturated NaHCO3
  5. dry with materialOrganics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was triturated in Et2O

Sources & evidence

ORD record
ord-b29d097b3d5c4f4792684365812731d3
Source dataset
uspto-grants-2016_03
Patent number
US09284307B2

Reaction notes

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