Triethylamine → 1-(3-chloro-4-methoxyphenyl)-N-(6'-methoxy-3,5'-dimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

HRID 870008Notes

Reaction equation

HRID 870008 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:13]([OH:15])=O)[CH2:12][CH2:11]2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].S(Cl)(Cl)=O.[CH3:20][O:21][C:22]1[N:27]=[CH:26][C:25]([C:28]2[C:33]([CH3:34])=[CH:32][CH:31]=[C:30]([NH2:35])[N:29]=2)=[CH:24][C:23]=1[CH3:36].CCN(CC)CC>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:13]([NH:35][C:30]3[N:29]=[C:28]([C:25]4[CH:26]=[N:27][C:22]([O:21][CH3:20])=[C:23]([CH3:36])[CH:24]=4)[C:33]([CH3:34])=[CH:32][CH:31]=3)=[O:15])[CH2:11][CH2:12]2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 591294641-(3-Chloro-4-methoxyphenyl)cyclopropane-1-carboxylic acidHCID 68722468HCID 68722468, compound

Product 1

HCID 687245221-(3-chloro-4-methoxyphenyl)-N-(6'-methoxy-3,5'-dimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamideYield 50.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-(3-chloro-4-methoxyphenyl)cyclopropanecarboxylic acid (45.3 mg, 0.2 mmol) in dichloromethane (2 mL) was added thionyl chloride (43.8 μL, 0.60 mmol) followed by DMF (1 drop) and the reaction was stirred at room temperature for 30 minutes and then the solvent was evaporated. Toluene (˜1 mL) was added and mixed with the residue and then evaporated. The residue 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 Et3N (83.6 μL, 0.60 mmol) in dichloromethane (1 mL) was added. The reaction was stirred at room temperature for 12 hours and then the reaction was then concentrated. The residue was dissolved in DMSO and purified by HPLC (10-99% acetonitrilein water) to yield 44 mg of the product. ESI-MS m/z calc. 437.1. found 438.1 (M+1)+. Retention time 2.10 minutes.

Workup

  1. customthe solvent was evaporated
  2. additionToluene (˜1 mL) was added
  3. additionmixed with the residue
  4. customevaporated
  5. dissolutionThe residue was then dissolved in dichloromethane (1 mL)
  6. stirringThe reaction was stirred at room temperature for 12 hours
  7. concentrationthe reaction was then concentrated
  8. dissolutionThe residue was dissolved in DMSO
  9. custompurified by HPLC (10-99% acetonitrilein water)

Sources & evidence

ORD record
ord-cd9cd6bf06cd4aceb1d5d3ea73ef9972
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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