2-Amino-4-methylthiazole → HCID 24820775, compound

HRID 552492Notes

Reaction equation

HRID 552492 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH3:7])[N:6]=1.C[Al](C)C.C[O:13][C:14]([C:16]1[CH:21]=[C:20]([C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=2)[N:19]=[C:18]([CH3:30])[N:17]=1)=O>O1CCOCC1.CCCCCC>[CH3:7][C:5]1[N:6]=[C:2]([NH:1][C:14]([C:16]2[CH:21]=[C:20]([C:22]3[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=3)[N:19]=[C:18]([CH3:30])[N:17]=2)=[O:13])[S:3][CH:4]=1

Participants

6

Reactant 3

HCID 741432-Amino-4-methylthiazoleHCID 16682925TrimethylaluminumHCID 67164287HCID 67164287, compound

Product 1

HCID 24820775HCID 24820775, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 156 mg (1.37 mmol, 1.8 equiv.) of 2-Amino-4-methylthiazole in 4 ml of dry dioxane were added 0.68 μl (1.37 mmol, 1.8 equiv.) of a 2M solution of trimethylaluminium in hexane. The solution was stirred for 1 h at room temperature. Then 200.0 mg (0.76 mmol) of 6-(3,5-Difluoro-phenyl)-2-methyl-pyrimidine-4-carboxylic acid methyl ester were added and the reaction was heated to 90° C. for 4 h. The reaction was quenched by cautious addition of 0.2 ml of water. Then approximately 1 g of anhydrous sodium sulfate were added to bind the water and the mixture was stirred vigorously for 5 min. The mixture was diluted by addition of 10 ml of methylenene chloride and filtered over Speedex filter aid which was washed with methylene chloride. The filtrate was concentrated in vaccuo and the residue was purified by flash chromatography (heptane/ethyl acetate 4:1) and recristallised from diisopropyl ether to yield the title compound (152.0 mg, 58%) as a white solid, MS (ISP): m/e=347.1 (M+H)+.

Workup

  1. temperaturethe reaction was heated to 90° C. for 4 h
  2. customThe reaction was quenched by cautious addition of 0.2 ml of water
  3. additionThen approximately 1 g of anhydrous sodium sulfate were added to bind the water
  4. stirringthe mixture was stirred vigorously for 5 min
  5. additionThe mixture was diluted by addition of 10 ml of methylenene chloride
  6. filtrationfiltered over Speedex
  7. filtrationfilter aid which
  8. washwas washed with methylene chloride
  9. concentrationThe filtrate was concentrated in vaccuo
  10. customthe residue was purified by flash chromatography (heptane/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-f79c706f85b1400d9b193f6c4ca5cb81
Source dataset
uspto-grants-2011_05
Patent number
US07951824B2

Reaction notes

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