Triethylamine → HCID 67397219, compound

HRID 912422Notes

Reaction equation

HRID 912422 reaction equation
[F:1][CH:2]([F:12])[C:3]1[C:7]([C:8](Cl)=[O:9])=[CH:6][N:5]([CH3:11])[N:4]=1.[S:13]1[CH:17]=[C:16]([CH2:18][NH:19][CH:20]2[CH2:22][CH2:21]2)[N:15]=[CH:14]1.C(N(CC)CC)C.CCCCC.C(OCC)(=O)C>O1CCCC1>[CH:20]1([N:19]([CH2:18][C:16]2[N:15]=[CH:14][S:13][CH:17]=2)[C:8]([C:7]2[C:3]([CH:2]([F:12])[F:1])=[N:4][N:5]([CH3:11])[CH:6]=2)=[O:9])[CH2:22][CH2:21]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 153401103-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chlorideHCID 22335286Ethyl acetate pentaneHCID 45121638HCID 45121638, compound

Product 1

HCID 67397219HCID 67397219, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

20 ml (0.29 mol) of cyclopropylamine was added to a solution of 4.9 g (29.0 mmol) of 4-(chloromethyl)-thiazole hydrochloride in 45 ml ethanol and 45 ml of saturated aqueous sodium hydrogen carbonate. The reaction mixture was stirred for 20 hrs at ambient temperature and extracted with ethyl acetate (3×100 ml). The combined organic layers were dried over magnesium sulphate and concentrated in vacuum. Column chromatography (gradient n-pentane/ethyl acetate) yielded 1.5 g (32% yield) of N-(1,3-thiazol-4-ylmethyl)cyclopropylamine. At ambient temperature a solution of 0.28 g (1.4 mmol) of 3-(difluoromethyl)-1-methyl-pyrazole-4-carbonyl chloride in 2 ml of tetrahydrofurane was added drop wise to a solution of 0.20 g (1.3 mmol) of N-(1,3-thiazol-4-ylmethyl)-cyclopropylamine and 0.6 ml triethylamine in 4 ml tetrahydrofurane. The reaction mixture was stirred for 16 hrs at ambient temperature and quenched with water. The watery layer was extracted three times with ethyl acetate (3×20 ml), the combined organic layers were dried over magnesium sulphate and concentrated in vacuum. Column chromatography (gradient n-pentane/ethyl acetate) yielded 0.13 mg (51% yield) of N-cyclopropyl-N-(1,3-thiazol-4-yl-methyl)-1-methyl-3-difluoromethyl-pyrazole-4-carboxamide (M+1=313).

Workup

  1. customquenched with water
  2. extractionThe watery layer was extracted three times with ethyl acetate (3×20 ml)
  3. dry with materialthe combined organic layers were dried over magnesium sulphate
  4. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-e1d2a16323b041f4a29914959fd86ec8
Source dataset
uspto-grants-2011_09
Patent number
US08026195B2

Reaction notes

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