Triethylamine → 1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-n-(6'-methoxy-3,5'-dimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

HRID 870012Notes

Reaction equation

HRID 870012 reaction equation
[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([C:11]3([C:14]([OH:16])=O)[CH2:13][CH2:12]3)[CH:9]=[CH:10][C:2]1=2.S(Cl)(Cl)=O.[CH3:21][O:22][C:23]1[N:28]=[CH:27][C:26]([C:29]2[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]([NH2:36])[N:30]=2)=[CH:25][C:24]=1[CH3:37].C(N(CC)CC)C>ClCCl.CN(C=O)C>[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([C:11]3([C:14]([NH:36][C:31]4[N:30]=[C:29]([C:26]5[CH:27]=[N:28][C:23]([O:22][CH3:21])=[C:24]([CH3:37])[CH:25]=5)[C:34]([CH3:35])=[CH:33][CH:32]=4)=[O:16])[CH2:12][CH2:13]3)[CH:9]=[CH:10][C:2]1=2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 431517731-(2,3-Dihydro-1,4-benzodioxin-6-yl)cyclopropanecarboxylic acidHCID 68722468HCID 68722468, compound

Product 1

HCID 687406131-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-n-(6'-methoxy-3,5'-dimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamideYield 18.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)cyclopropanecarboxylic acid (44.04 mg, 0.2 mmol) in dichloromethane (2 mL) was added thionyl chloride (14.6 μL, 0.20 mmol) followed by DMF (1 drop) and the reaction was stirred at room temperature for 30 minutes. The solvent was removed by rotovap. Toluene (˜1 mL) was added and mixed with the residue and then removed by rotovap. The toluene step was repeated once more 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 (46 mg, 0.20 mmol) and triethylamine (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 16 mg of the product. ESI-MS m/z calc. 431.2. found 432.5 (M+1)+. Retention time 1.98 minutes.

Workup

  1. customThe solvent was removed by rotovap
  2. additionToluene (˜1 mL) was added
  3. additionmixed with the residue
  4. customremoved by rotovap
  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-050bddf62f07418088240756d1dd83b4
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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