Oxalyl chloride → 1-(3-chloro-2-pyridinyl)-N-[2-methyl-6-[2-[(1-methylethyl)amino]-2-oxoethyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

HRID 905519Notes

Reaction equation

HRID 905519 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([OH:15])=O)=[CH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[NH2:26][C:27]1[C:32]([CH3:33])=[CH:31][CH:30]=[CH:29][C:28]=1[CH2:34][C:35]([NH:37][CH:38]([CH3:40])[CH3:39])=[O:36].C(N(CC)C(C)C)(C)C>ClCCl.CN(C)C=O.CN(C)C1C=CN=CC=1.O1CCCC1>[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([NH:26][C:27]3[C:28]([CH2:34][C:35]([NH:37][CH:38]([CH3:39])[CH3:40])=[O:36])=[CH:29][CH:30]=[CH:31][C:32]=3[CH3:33])=[O:15])=[CH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 113921841-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acidHCID 673906992-amino-3-methyl-N-(1-methylethyl)benzeneacetamide2×

Product 1

HCID 160977431-(3-chloro-2-pyridinyl)-N-[2-methyl-6-[2-[(1-methylethyl)amino]-2-oxoethyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a slurry of 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (for preparation see WO 02/48115, 0.19 g, 0.66 mmol) in 10 mL of dichloromethane was added oxalyl chloride (0.087 mL, 1.0 mmol) and two drops of N,N-dimethylformamide. The reaction mixture was stirred for 15 minutes, resulting in a solution. The volatiles were removed with a rotary evaporator. The residue was dissolved in 10 mL of tetrahydrofuran, and the solution was added dropwise at 0° C. to 2-amino-3-methyl-N-(1-methylethyl)-benzeneacetamide (i.e. the title product of Step B) (0.14 g, 0.66 mmol), N,N-diisopropyl-ethylamine, (0.23 mL, 1.3 mmol) and 4-(dimethylamino)pyridine (5 mg) in 5 mL of tetrahydrofuran. The reaction mixture was stirred overnight at room temperature. Dichloromethane was added and the mixture was washed with water and dried (sodium sulfate). The solvent was removed with a rotary evaporator. The residue was purified by MPLC (40→60% ethyl acetate in hexanes as eluant) to afford the title compound plus an impurity. The material was purified further by MPLC (20→30% ethyl acetate in 1-chlorobutane as eluant) to afford the title product, a compound of the present invention, as a white solid (0.12 g), m.p. 206-207° C.

Workup

  1. customresulting in a solution
  2. customThe volatiles were removed with a rotary evaporator
  3. dissolutionThe residue was dissolved in 10 mL of tetrahydrofuran
  4. stirringThe reaction mixture was stirred overnight at room temperature
  5. washthe mixture was washed with water
  6. dry with materialdried (sodium sulfate)
  7. customThe solvent was removed with a rotary evaporator
  8. customThe residue was purified by MPLC (40→60% ethyl acetate in hexanes as eluant)

Sources & evidence

ORD record
ord-8da6637950964301be76ef8c7046d834
Source dataset
uspto-grants-2011_09
Patent number
US08012499B2

Reaction notes

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