Triethylamine → N-[(3-chlorobiphenyl-4-yl)methyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide

HRID 631024Notes

Reaction equation

HRID 631024 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].[Cl:12][C:13]1[CH:14]=[C:15]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:16]=[CH:17][C:18]=1[CH2:19][NH:20][CH:21]1[CH2:23][CH2:22]1.C(N(CC)CC)C>O1CCCC1>[Cl:12][C:13]1[CH:14]=[C:15]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:16]=[CH:17][C:18]=1[CH2:19][N:20]([CH:21]1[CH2:22][CH2:23]1)[C:9]([C:3]1[C:4]([CH3:8])=[N:5][N:6]([CH3:7])[C:2]=1[F:1])=[O:10]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 108668795-Fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chlorideHCID 67071683N-[(3-chlorobiphenyl-4-yl)methyl]cyclopropanamine

Product 1

HCID 44816052N-[(3-chlorobiphenyl-4-yl)methyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamideYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

At ambient temperature, a solution of 226 mg (1.28 mmol) of 5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chloride in 1 ml of tetrahydrofurane is added dropwise to a solution of 300 mg (1.164 mmol) of N-[(3-chlorobiphenyl-4-yl)methyl]cyclopropanamine and 0.18 ml of triethylamine in 5 ml tetrahydrofurane. The reaction mixture is stirred for 15 hrs at room temperature. 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 (2×50 ml) and the combined organic layers are successively washed by a 1M solution of HCl, a saturated solution of potassium carbonate and brine and filtered over a ChemElut cartridge to yield after concentration 350 mg (72% yield) of N-[(3-chlorobiphenyl-4-yl)methyl]-N-cyclopropyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide as a yellow oil (M+H=398).

Workup

  1. customThe solvent is removed under vacuum and 10 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 1M solution of HCl
  5. filtrationa saturated solution of potassium carbonate and brine and filtered over a ChemElut cartridge

Sources & evidence

ORD record
ord-721b9b2e6ee34a84afa78c9f1e3da97f
Source dataset
uspto-grants-2016_04
Patent number
US09320277B2

Reaction notes

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