Triethylamine → HCID 44595546, compound

HRID 467972Notes

Reaction equation

HRID 467972 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.Cl.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([C@@H:23]2[CH2:27][CH2:26][CH2:25][NH:24]2)=[O:22])=[CH:17][CH:16]=1.C(N(CC)CC)C>ClCCl>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([C@@H:23]2[CH2:27][CH2:26][CH2:25][N:24]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])=[O:22])=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 153401103-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chlorideHCID 44595680HCID 44595680, compound

Product 1

HCID 44595546HCID 44595546, compoundYield 97.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

At a temperature of 0° C., a solution of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (1.94 g; 10.0 mmol) in dichloromethane (5 ml) was added dropwise to a stirred suspension of (4-chloro-phenyl)-(S)-pyrrolidin-2-yl-methanone hydrochloride (2.46 g; 10.0 mmol), which was prepared as described in example P16, and triethylamine (3.0 g; 30.0 mmol) in dichloromethane (25 ml). Dichloromethane (40 ml) was added to the mixture. The ice bath was removed and reaction mixture was allowed stirring for 3 hours. The reaction mixture was washed with 1M NaOH (20 ml), 1M HCl (20 ml) and saturated NaCl (20 ml) and then dried over Na2SO4. After removal of the solvent, the residue was purified by flash chromatography over silica gel (eluent:cyclohexane/ethyl acetate 1:19). 3.58 g (97.3% of theory) of (4-chloro-phenyl)-[(S)-1-(3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl)-pyrrolidin-2-yl]-methanone was obtained in form of an oil. 1H NMR (400 MHz, CDCl3): δ 1.91-1.98 (m, 1H), 2.02-2.16 (m, 2H), 2.33-2.42 (m, 1H), 3.75-3.85 (m, 2H), 3.97 (s, 3H, NCH3), 5.61-5.65 (m, 1H), 6.99-7.28 (t, 1H, CHF2), 7.45-7.47 (d, 2H, Ar—H), 7.73 (s, 1H) 7.96-7.98 (d, 2H, Ar—H). MS [M+H]+ 368/370.

Workup

  1. customwas prepared
  2. customThe ice bath was removed
  3. customreaction mixture
  4. washThe reaction mixture was washed with 1M NaOH (20 ml), 1M HCl (20 ml) and saturated NaCl (20 ml)
  5. dry with materialdried over Na2SO4
  6. customAfter removal of the solvent
  7. customthe residue was purified by flash chromatography over silica gel (eluent:cyclohexane/ethyl acetate 1:19)

Sources & evidence

ORD record
ord-c1c54574b66640c1894335b917662352
Source dataset
uspto-grants-2014_01
Patent number
US08623902B2

Reaction notes

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