Triethylamine → n-(6'-Methoxy-3,5'-dimethyl-2,3'-bipyridin-6-yl)-1-(3-methoxyphenyl)cyclopropanecarboxamide

HRID 870014Notes

Reaction equation

HRID 870014 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2([C:12]([OH:14])=O)[CH2:11][CH2:10]2)[CH:6]=[CH:7][CH:8]=1.S(Cl)(Cl)=O.[CH3:19][O:20][C:21]1[N:26]=[CH:25][C:24]([C:27]2[C:32]([CH3:33])=[CH:31][CH:30]=[C:29]([NH2:34])[N:28]=2)=[CH:23][C:22]=1[CH3:35].C(N(CC)CC)C>ClCCl.CN(C=O)C>[CH3:19][O:20][C:21]1[N:26]=[CH:25][C:24]([C:27]2[C:32]([CH3:33])=[CH:31][CH:30]=[C:29]([NH:34][C:12]([C:9]3([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=4)[CH2:10][CH2:11]3)=[O:14])[N:28]=2)=[CH:23][C:22]=1[CH3:35]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 288754611-(3-Methoxyphenyl)cyclopropane-1-carboxylic acidHCID 68722468HCID 68722468, compound

Product 1

HCID 91614187n-(6'-Methoxy-3,5'-dimethyl-2,3'-bipyridin-6-yl)-1-(3-methoxyphenyl)cyclopropanecarboxamideYield 50.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

1-(3-Methoxyphenyl)cyclopropanecarboxylic acid (38.4 mg, 0.2 mmol) was dissolved in dichloromethane (2 mL) and thionyl chloride (43.8 μL, 0.60 mmol) was added followed by DMF (1 drop) and the reaction was stirred at room temperature for 30 minutes. Then the solvent was removed by evaporation, toluene (˜1 mL) was added twice, mixed with the residue and removed by evaporation and then the residue was placed under high vacuum for 10 minutes. It was then dissolved in dichloromethane (1 mL) and a solution of 6′-methoxy-3,5′-dimethyl-2,3′-bipyridin-6-amine (45.9 mg, 0.20 mmol) and triethyl amine (83.6 μL, 0.60 mmol) in dichloromethane (1 mL) was added. The reaction was stirred at room temperature for 12 hours. The reaction was then concentrated. The residue was dissolved in DMSO and purified by reverse phase HPLC (10-99% CH3CN in water) to yield 41 mg (50% yield) of the product. ESI-MS m/z calc. 403.5. found 404.5 (M+1)+. Retention time 2.03 minutes.

Workup

  1. customThen the solvent was removed by evaporation, toluene (˜1 mL)
  2. additionwas added twice
  3. additionmixed with the residue
  4. customremoved by evaporation
  5. waitthe residue was placed under high vacuum for 10 minutes
  6. dissolutionIt was then dissolved in dichloromethane (1 mL)
  7. stirringThe reaction was stirred at room temperature for 12 hours
  8. concentrationThe reaction was then concentrated
  9. dissolutionThe residue was dissolved in DMSO
  10. custompurified by reverse phase HPLC (10-99% CH3CN in water)

Sources & evidence

ORD record
ord-739a9389c05c47c68836835f3aa21605
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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