Triethylamine → 1-(4-Chlorophenyl)-n-(5-methyl-6-(5-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide

HRID 870007Notes

Reaction equation

HRID 870007 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.C[O:19][C:20]1[N:25]=[CH:24][C:23]([C:26]2[C:31]([CH3:32])=[CH:30][CH:29]=[C:28]([NH2:33])[N:27]=2)=[CH:22][C:21]=1[CH3:34].C(N(CC)CC)C>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:11]([NH:33][C:28]3[CH:29]=[CH:30][C:31]([CH3:32])=[C:26]([C:23]4[CH:22]=[C:21]([CH3:34])[C:20](=[O:19])[NH:25][CH:24]=4)[N:27]=3)=[O:13])[CH2:9][CH2:10]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 986061-(p-Chlorophenyl)cyclopropanecarboxylic acidHCID 68722468HCID 68722468, compound

Product 1

HCID 710530451-(4-Chlorophenyl)-n-(5-methyl-6-(5-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamideYield 78.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-(4-chlorophenyl)cyclopropanecarboxylic acid (39.3 mg, 0.2 mmol) in dichloromethane (2 mL) was added thionyl chloride (43.8 μL, 0.6 mmol) followed by DMF (1 drop) and the reaction was stirred at room temperature for 30 minutes and then the solvent was removed. Toluene (˜1 mL) was added, mixed with the residue and then removed by evaporation. The residue was then dissolved in dichloromethane (1 mL) and a solution of 6′-methoxy-3,5′-dimethyl-2,3′-bipyridin-6-amine (46 mg, 0.2 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 hors. The reaction was then concentrated. The residue was dissolved in DMSO and purified by reverse phase HPLC (10-99% acetonitrile/water) to yield 62 mg of the product. ESI-MS m/z calc. 407.1. found 408.2 (M+1)+. Retention time 2.07 minutes.

Workup

  1. customthe solvent was removed
  2. additionToluene (˜1 mL) was added
  3. additionmixed with the residue
  4. customremoved by evaporation
  5. dissolutionThe residue was then dissolved in dichloromethane (1 mL)
  6. stirringThe reaction was stirred at room temperature for 12 hors
  7. concentrationThe reaction was then concentrated
  8. dissolutionThe residue was dissolved in DMSO
  9. custompurified by reverse phase HPLC (10-99% acetonitrile/water)

Sources & evidence

ORD record
ord-7c2ae0741bdf4151ad65887395542f20
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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