Triethylamine → cis-N-cyclopropyl-5-fluoro-1,3-dimethyl-N-(2-phenylcyclohexyl)-1H-pyrazole-4-carboxamide

HRID 387239Notes

Reaction equation

HRID 387239 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].[CH:12]1([NH:15][C@@H:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C@@H:17]2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:14][CH2:13]1.C(N(CC)CC)C>O1CCCC1>[CH:12]1([N:15]([C@@H:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C@@H:17]2[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:9]([C:3]2[C:4]([CH3:8])=[N:5][N:6]([CH3:7])[C:2]=2[F:1])=[O:10])[CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 108668795-Fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chlorideHCID 71251557cis-N-cyclopropyl-2-phenylcyclohexanamine

Product 1

HCID 71251560cis-N-cyclopropyl-5-fluoro-1,3-dimethyl-N-(2-phenylcyclohexyl)-1H-pyrazole-4-carboxamideYield 48.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

At ambient temperature, a solution of 180 mg (1.02 mmol) of 5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chloride in 1 ml of tetrahydrofurane is added dropwise to a solution of 200 mg (0.93 mmol) of cis-N-cyclopropyl-2-phenylcyclohexanamine and 100 mg (1.02 mmol) of triethylamine in 5 ml of tetrahydrofurane. The reaction mixture is stirred for 2 hrs at 70° C. The solvent is removed under vacuum and 100 ml of water are then added to the residue. The watery layer is extracted twice with ethyl acetate (2×50 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 over a Chemelut™ cartridge to yield after concentration 380 mg of a yellow oil. Column chromatography on silica gel (gradient heptane/ethyl acetate) yields 160 mg (46% yield) of cis-N-cyclopropyl-5-fluoro-1,3-dimethyl-N-(2-phenylcyclohexyl)-1H-pyrazole-4-carboxamide as a colorless oil (M+H=356).

Workup

  1. customThe solvent is removed under vacuum and 100 ml of water
  2. additionare then added to the residue
  3. extractionThe watery layer is extracted twice with ethyl acetate (2×50 ml)
  4. washthe combined organic layers are successively washed by a 1 N solution of HCl
  5. dry with materiala saturated solution of potassium carbonate and brine and dried over a Chemelut™ cartridge
  6. customto yield after concentration 380 mg of a yellow oil

Sources & evidence

ORD record
ord-bb22ae089c92417da4b5272c07deb685
Source dataset
uspto-grants-2013_02
Patent number
US08372982B2

Reaction notes

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