Acetic Acid → 4-bromo-2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiazole

HRID 2091617Notes

Reaction equation

HRID 2091617 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:7]([NH:9][NH2:10])=O)[S:5][CH:6]=1.[CH:11]1([NH2:14])[CH2:13][CH2:12]1.[C:15](O)(=O)C>C1(C)C=CC=CC=1>[Br:1][C:2]1[N:3]=[C:4]([C:7]2[N:14]([CH:11]3[CH2:13][CH2:12]3)[CH:15]=[N:10][N:9]=2)[S:5][CH:6]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 69828CyclopropylamineHCID 580356604-Bromothiazole-2-carbohydrazide

Product 1

HCID 580356534-bromo-2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiazoleYield 97.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

The 4-bromothiazole-2-carbohydrazide (620 mg, 2.8 mmol) and toluene (9 mL) were added to a sealable vial, and N,N-dimethylformamide/N,N-dimethylacetamide complex (920 μL, 6.9 mmol) was added. The mixture was stirred for 5 minutes, then cyclopropyl amine (770 μL, 11 mmol), and acetic acid (160 μL, 2.8 mmol) were added, and the reaction was heated in a microwave reactor at 150° C. for 30 minutes. The solvent was removed under reduced pressure, and the residue purified by flash chromatography (1→7% methanol in methylene chloride) to afford 740 mg of 4-bromo-2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiazole (contaminated with DMF•DMA, but used directly in next step).

Workup

  1. additionwas added
  2. customThe solvent was removed under reduced pressure
  3. customthe residue purified by flash chromatography (1→7% methanol in methylene chloride)

Sources & evidence

ORD record
ord-a4477625c1ab4a20aebfdd909fd09728
Source dataset
uspto-grants-2013_05
Patent number
US08440665B2

Reaction notes

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