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

HRID 870010Notes

Reaction equation

HRID 870010 reaction equation
[CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3([C:13]([OH:15])=O)[CH2:12][CH2:11]3)=[CH:7][CH:8]=2)[CH2:3][O:2]1.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>[CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3([C:13]([NH:35][C:30]4[N:29]=[C:28]([C:25]5[CH:26]=[N:27][C:22]([O:21][CH3:20])=[C:23]([CH3:36])[CH:24]=5)[C:33]([CH3:34])=[CH:32][CH:31]=4)=[O:15])[CH2:11][CH2:12]3)=[CH:7][CH:8]=2)[CH2:3][O:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 59129550HCID 59129550, compoundHCID 68722468HCID 68722468, compound

Product 1

HCID 687244141-(1,3-Dihydroisobenzofuran-5-yl)-N-(6'-methoxy-3,5'-dimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamideYield 48.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-(1,3-dihydroisobenzofuran-5-yl)cyclopropanecarboxylic acid (40.8 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 removed by rotovap. The residue was then dissolved in dichloromethane (1 mL) and a solution of 6′-methoxy-3,5′-dimethyl-2,3′-bipyridin-6-amine (45.8 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. The reaction was then concentrated. The residue was dissolved in DMSO and purified by reverse phase HPLC (10-99% CH3CN in water) to yield 40 mg of the desired product. ESI-MS m/z calc. 415.2. found 416.5 (M+1)+. Retention time 1.87 minutes.

Workup

  1. customthe solvent was evaporated
  2. additionToluene (˜1 mL) was added
  3. additionmixed with the residue
  4. customremoved by rotovap
  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 reverse phase HPLC (10-99% CH3CN in water)

Sources & evidence

ORD record
ord-0763fec9a8e941a089ec293e632b7fe8
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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