Trifluoroacetic acid → HCID 25120802, compound

HRID 2354941Notes

Reaction equation

HRID 2354941 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:12]([OH:14])=O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.S(Cl)(Cl)=O.C(N(CC)CC)C.[NH2:26][C:27]1[N:32]=[C:31]([C:33]2[CH:34]=[C:35]([CH:43]=[CH:44][CH:45]=2)[C:36]([O:38]C(C)(C)C)=[O:37])[C:30]([CH3:46])=[CH:29][CH:28]=1.FC(F)(F)C(O)=O>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2([C:12]([NH:26][C:27]3[N:32]=[C:31]([C:33]4[CH:34]=[C:35]([CH:43]=[CH:44][CH:45]=4)[C:36]([OH:38])=[O:37])[C:30]([CH3:46])=[CH:29][CH:28]=3)=[O:14])[CH2:10][CH2:11]2)=[CH:7][CH:8]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 855751-(4-Methoxyphenyl)cyclopropane-1-carboxylic acidHCID 45480517Benzoic acid, 3-(6-amino-3-methyl-2-pyridinyl)-, 1,1-dimethylethyl ester

Product 1

HCID 25120802HCID 25120802, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(4-Methoxyphenyl)cyclopropanecarboxylic acid (57.7 mg, 0.300 mmol) was placed in an oven-dried flask which was allowed to cool under nitrogen. Thionyl chloride (0.3 mL) and N,N-dimethylformamide (0.03 mL) were added and the solution was allowed to stir for 30 minutes. The excess thionyl chloride was removed under vacuum and the resulting oil was re-dissolved in dichloromethane containing triethylamine (0.125 mL, 0.900 mmol). tert-Butyl 3-(6-amino-3-methylpyridin-2-yl)benzoate (85.3 mg, 0.300 mmol) was added and the reaction mixture was allowed to stir for 3 hours. Trifluoroacetic acid (1 mL) was added and the solution was allowed to stir for an additional 3 hours. The mixture was evaporated to dryness, dissolved in a minimum of N,N-dimethylformamide and then purified by reverse-phase preparative liquid chromatography utilizing a gradient of 0-99% acetonitrile in water containing 0.05% trifluoroacetic acid to yield 3-(6-(1-(4-methoxyphenyl)cyclopropane carboxamido)-3-methylpyridin-2-yl)benzoic acid. ESI-MS m/z calc. 402.2, found; 403.1 (M+1)+ Retention time 1.65 minutes.

Workup

  1. temperatureto cool under nitrogen
  2. customThe excess thionyl chloride was removed under vacuum
  3. dissolutionthe resulting oil was re-dissolved in dichloromethane
  4. stirringto stir for 3 hours
  5. stirringto stir for an additional 3 hours
  6. customThe mixture was evaporated to dryness
  7. dissolutiondissolved in a minimum of N,N-dimethylformamide
  8. custompurified by reverse-phase preparative liquid chromatography

Sources & evidence

ORD record
ord-eaefd78888ae448e9a70fe77e573d2cb
Source dataset
uspto-grants-2010_07
Patent number
US07754739B2

Reaction notes

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