Triethylamine → N-[2-(biphenyl-4-yloxy)ethyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide

HRID 77693Notes

Reaction equation

[F:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([CH3:8])[C:3]=1[C:9](Cl)=[O:10].[C:12]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][NH:21][CH:22]2[CH2:24][CH2:23]2)=[CH:14][CH:13]=1.C(N(CC)CC)C.CCCCCCC.C(OCC)(=O)C>O1CCCC1>[C:12]1([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][N:21]([CH:22]2[CH2:24][CH2:23]2)[C:9]([C:3]2[C:4]([CH3:8])=[N:5][N:6]([CH3:7])[C:2]=2[F:1])=[O:10])=[CH:14][CH:13]=1

Participants

Conditions

Temperature: 80 °C

Procedure

At ambient temperature, a solution of 230 mg (1.29 mmol) of 5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chloride in 1 ml of tetrahydrofurane is added dropwise to a mixture of 300 mg (1.18 mmol) of N-[2-(biphenyl-4-yloxy)ethyl]cyclopropanamine as its hydrochloride salt and 250 mg (2.48 mmol) of triethylamine in 5 ml of tetrahydrofurane. The reaction mixture is stirred for 2 hrs at 80° C. The solvent is removed under vacuum and 10 ml of water are then added to the residue. The watery layer is extracted twice with ethyl acetate (2×25 ml) and the combined organic layers are successively washed by a 1 N solution of HCl, a saturated solution of potassium carbonate and brine and dried of magnesium sulfate to gave after concentration 750 mg of a yellow oil. Column chromatography (gradient heptane/ethyl acetate) yielded 220 mg (47% yield) of N-[2-(biphenyl-4-yloxy)ethyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide as a colourless oil (M+H=394).

Workup

customThe solvent is removed under vacuum and 10 ml of water
additionare then added to the residue
extractionThe watery layer is extracted twice with ethyl acetate (2×25 ml)
washthe combined organic layers are successively washed by a 1 N solution of HCl
dry with materiala saturated solution of potassium carbonate and brine and dried of magnesium sulfate
customto gave after concentration 750 mg of a yellow oil

Sources & evidence

ORD record: ord-a75bfc9af4ef48eba05ebfdd706ba5e9
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841332B2

Reaction notes

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