Ammonium Chloride → Methyl 4-chloro-3-[(3-{[(2,6-difluorophenyl)carbonyl]amino}-1H-pyrazol-1-yl)methyl]benzoate

HRID 1946313Notes

Reaction equation

HRID 1946313 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[F:11][C:12]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:13]=1[C:14]([NH:16][C:17]1[CH:21]=[CH:20][NH:19][N:18]=1)=[O:15].Br[CH2:28][C:29]1[CH:30]=[C:31]([CH:36]=[CH:37][C:38]=1[Cl:39])[C:32]([O:34][CH3:35])=[O:33].[Cl-].[NH4+]>C1COCC1.C(C1C=CC=CC=1)C.C1COCC1>[Cl:39][C:38]1[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][C:29]=1[CH2:28][N:19]1[CH:20]=[CH:21][C:17]([NH:16][C:14]([C:13]2[C:22]([F:26])=[CH:23][CH:24]=[CH:25][C:12]=2[F:11])=[O:15])=[N:18]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 12144656Methyl 3-(bromomethyl)-4-chlorobenzoateHCID 178522346HCID 178522346, compound

Product 1

HCID 59547941Methyl 4-chloro-3-[(3-{[(2,6-difluorophenyl)carbonyl]amino}-1H-pyrazol-1-yl)methyl]benzoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 68569164HCID 68569164, compoundSolvent

Procedure

1.0 M LiHMDS (5.00 ml, 5.00 mmol) in THF/ethylbenzene was added slowly to a solution of 2,6-difluoro-N-(1H-pyrazol-3-yl)benzamide (for a preparation see Intermediate 9)(1.12 g, 5 mmol) in THF (50 ml) under nitrogen at ambient temperature. The solution was stirred for 20 min and a solution of methyl 3-(bromomethyl)-4-chlorobenzoate (1.32 g, 5.0 mmol, synthesised according to WO2006079857) in THF (4 ml) was added in one portion. The solution was stirred for 2 h and left overnight. The solution was treated with aqueous ammonium chloride (50 ml) and extracted with ethyl acetate (2×50 ml). The combined organic extracts were dried (Na2SO4), filtered and solvent evaporated in vacuo. The residue was purified on a silica cartridge (50 g) eluted with 0-100% cyclohexane/EtOAc to give the title compound (1.95 g) as a white solid after evaporation from diethyl ether; LCMS: (System 4) MH+=406/408, tRET=2.69 min.

Workup

  1. customat ambient temperature
  2. stirringThe solution was stirred for 2 h
  3. waitleft overnight
  4. extractionextracted with ethyl acetate (2×50 ml)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. customsolvent evaporated in vacuo
  8. customThe residue was purified on a silica cartridge (50 g)
  9. washeluted with 0-100% cyclohexane/EtOAc

Sources & evidence

ORD record
ord-cd2407bba64045388dbbd2330cbafdc9
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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