Sodium Hydroxide → diethyl [4-({(2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]prop-2-enoyl}amino)benzyl]phosphonate

HRID 30723Notes

Reaction equation

HRID 30723 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:13])[N:11]=[CH:10][C:9]=2/[CH:14]=[CH:15]/[C:16]([OH:18])=O)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH2:23][C:24]1[CH:38]=[CH:37][C:27]([CH2:28][P:29](=[O:36])([O:33][CH2:34][CH3:35])[O:30][CH2:31][CH3:32])=[CH:26][CH:25]=1.C(N(C(C)C)CC)(C)C.[OH-].[Na+]>O.CN(C)C=O.C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([CH3:13])[N:11]=[CH:10][C:9]=2/[CH:14]=[CH:15]/[C:16]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([CH2:28][P:29](=[O:36])([O:30][CH2:31][CH3:32])[O:33][CH2:34][CH3:35])=[CH:37][CH:38]=2)=[O:18])=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 88358Diethyl p-aminobenzylphosphonateHCID 69208981(2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]acrylic acid

Product 1

HCID 24811215diethyl [4-({(2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]prop-2-enoyl}amino)benzyl]phosphonateYield 92%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a mixture of (2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]acrylic acid (35.0 g), acetonitrile (245 mL) and dimethylformamide (0.175 mL) was added thionyl chloride (11.4 mL) at 40-45° C. and the mixture was stirred for 1 hr. Then diethyl 4-aminobenzylphosphonate (36.3 g) was added at 5° C. and diisopropylethylamine (61.9 mL) was further added dropwise. The mixture was stirred at room temperature for 1 hr. A 1N aqueous sodium hydroxide solution (140 mL) was added to neutralize the reaction mixture and water (472.5 mL) was further added. The mixture was stirred at room temperature for 1 hr. The precipitated crystals were collected by filtration and washed with 30% acetonitrile to give diethyl [4-({(2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]prop-2-enoyl}amino)benzyl]phosphonate (61.5 g, yield 92%).

Workup

  1. stirringThe mixture was stirred at room temperature for 1 hr
  2. additionwas further added
  3. stirringThe mixture was stirred at room temperature for 1 hr
  4. filtrationThe precipitated crystals were collected by filtration
  5. washwashed with 30% acetonitrile

Sources & evidence

ORD record
ord-30212eeeda4043e3a529b20fbb5fdb4d
Source dataset
uspto-grants-2008_09
Patent number
US07423159B2

Reaction notes

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