Trifluoroacetic acid → HCID 25120803, compound

HRID 2354946Notes

Reaction equation

HRID 2354946 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([OH:15])=O)[CH2:12][CH2:11]3)=[CH:9][C:4]=2[CH2:3][CH2:2]1.S(Cl)(Cl)=O.C(N(CC)CC)C.[NH2:27][C:28]1[N:33]=[C:32]([C:34]2[CH:35]=[C:36]([CH:44]=[CH:45][CH:46]=2)[C:37]([O:39]C(C)(C)C)=[O:38])[C:31]([CH3:47])=[CH:30][CH:29]=1.FC(F)(F)C(O)=O>CN(C)C=O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:27][C:28]4[N:33]=[C:32]([C:34]5[CH:35]=[C:36]([CH:44]=[CH:45][CH:46]=5)[C:37]([OH:39])=[O:38])[C:31]([CH3:47])=[CH:30][CH:29]=4)=[O:15])[CH2:11][CH2:12]3)=[CH:9][C:4]=2[CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 45480517Benzoic acid, 3-(6-amino-3-methyl-2-pyridinyl)-, 1,1-dimethylethyl esterHCID 513584551-(2,3-Dihydrobenzofuran-5-yl)cyclopropanecarboxylic acid

Product 1

HCID 25120803HCID 25120803, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(2,3-Dihydrobenzofuran-5-yl)cyclopropanecarboxylic acid (24.0 mg, 0.118 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 (0.0495 mL, 0.353 mmol). tert-Butyl 3-(6-amino-3-methylpyridin-2-yl)benzoate (33.4 mg, 0.118 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-(2,3-dihydrobenzofuran-5-yl)cyclo-propanecarboxamido)-3-methylpyridin-2-yl)benzoic acid. ESI-MS m/z calc. 414.2, found; 415.0 (M+1)+ Retention time 1.64 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-0d4f2fd547ff44d38ec513fd5de72a67
Source dataset
uspto-grants-2010_07
Patent number
US07754739B2

Reaction notes

Loading…