Dichloromethane → 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [3-(4-methoxy-benzylamino)-5-(2-trifluoromethyl-phenyl)-pyrazin-2-yl]-amide

HRID 1481547Notes

Reaction equation

HRID 1481547 reaction equation
Br[C:2]1[N:3]=[C:4]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[C:5]([NH:8][C:9]([C:11]2[N:12]([CH3:21])[N:13]=[C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:15]=2[Cl:16])=[O:10])=[N:6][CH:7]=1.[F:32][C:33]([F:44])([F:43])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1B(O)O.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C1(C)C=CC=CC=1>[CH3:31][O:30][C:27]1[CH:28]=[CH:29][C:24]([CH2:23][NH:22][C:4]2[C:5]([NH:8][C:9]([C:11]3[N:12]([CH3:21])[N:13]=[C:14]([C:17]([CH3:19])([CH3:18])[CH3:20])[C:15]=3[Cl:16])=[O:10])=[N:6][CH:7]=[C:2]([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=3[C:33]([F:44])([F:43])[F:32])[N:3]=2)=[CH:25][CH:26]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 866574125-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [5-bromo-3-(4-methoxy-benzylamino)-pyrazin-2-yl]-amide

Product 1

HCID 674122355-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [3-(4-methoxy-benzylamino)-5-(2-trifluoromethyl-phenyl)-pyrazin-2-yl]-amide

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [5-bromo-3-(4-methoxy-benzylamino)-pyrazin-2-yl]-amide (87 mg, 0.17 mmol), 2-trifluoromethyl-phenylboronic acid (36 mg, 0.19 mmol), in DMF (0.5 mL), toluene (2 mL) and water (2 mL), K2CO3 (33 mg, 0.23 mmol) was added. The resulting solution was placed under Ar and (dppf)PdCl2.DCM (14 mg, 0.02 mmol) was added. The resulting mixture was stirred at 100° C. overnight. The organic layer was separated, dried (Na2SO4) and concentrated. The residue obtained was purified on silica (20:80-100:0 EtOAc: hexane) to yield 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [3-(4-methoxy-benzylamino)-5-(2-trifluoromethyl-phenyl)-pyrazin-2-yl]-amide. Mass Spectrum (LCMS, ESI pos.): Calculated for C28H28ClF3N6O: 573.1 (M+H). Measured: 573.3.

Workup

  1. customThe organic layer was separated
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue obtained
  5. customwas purified on silica (20:80-100:0 EtOAc: hexane)

Sources & evidence

ORD record
ord-86b8c8e8dca743c382f3332727421b25
Source dataset
uspto-grants-2016_08
Patent number
US09409915B2

Reaction notes

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