2,6-Lutidine → N-[1-({2-Chloro-4-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]-2,6-difluorobenzamide

HRID 1946370Notes

Reaction equation

HRID 1946370 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][NH:9][N:8]=1)=[O:5].Br[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:21][C:20]=1[Cl:33].N1C(C)=CC=CC=1C>CN1C(=O)CCC1>[Cl:33][C:20]1[CH:21]=[C:22]([O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:23]=[CH:24][C:19]=1[CH2:18][N:9]1[CH:10]=[CH:11][C:7]([NH:6][C:4](=[O:5])[C:3]2[C:12]([F:16])=[CH:13][CH:14]=[CH:15][C:2]=2[F:1])=[N:8]1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 66770473HCID 66770473, compoundHCID 178522346HCID 178522346, compound2×

Product 1

HCID 59547945N-[1-({2-Chloro-4-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]-2,6-difluorobenzamide

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of 2,6-difluoro-N-(1H-pyrazol-3-yl)benzamide (for a preparation see Intermediate 9)(0.961 g, 4.31 mmol) and 1-(bromomethyl)-2-chloro-4-[(phenylmethyl)oxy]benzene (1.21 g, 3.88 mmol) in anhydrous NMP (15 ml) was added 2,6-lutidine (0.5 ml, 4.29 mmol, Aldrich). The reaction vessel (20 ml) was sealed and heated in Biotage Initiator microwave to 160° C. for 30 min. After cooling the reaction mixture was partitioned between saturated aqueous sodium hydrogen carbonate (120 ml) and ethyl acetate (100 ml). The phases were separated and the aqueous phase extracted with ethyl acetate (50 ml). The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (50 ml), dried (MgSO4), filtered and the solvent removed in vacuo to leave a red oil (2.84 g). The residue was loaded in dichloromethane and purified on silica (100 g×2) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white solid (0.778 g); LCMS: (System 4) MH+=454, tRET=3.35 min.

Workup

  1. customThe reaction vessel (20 ml) was sealed
  2. temperatureAfter cooling the reaction mixture
  3. customwas partitioned between saturated aqueous sodium hydrogen carbonate (120 ml) and ethyl acetate (100 ml)
  4. customThe phases were separated
  5. extractionthe aqueous phase extracted with ethyl acetate (50 ml)
  6. washThe combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (50 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-f2fca628f23147f08d8fd95425e5dffc
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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