Methyl Acetate → 3-(2-Allyl-1-oxo-1,2-dihydro-isoquinolin-6-yl)-n-cyclopropyl-4-methyl-benzamide

HRID 907254Notes

Reaction equation

HRID 907254 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10]C)=O)=[CH:6][C:5]=1[C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[C:20](=[O:24])[NH:19][CH:18]=[CH:17]2.C(OC)(=O)C.[CH2:30](Br)[CH:31]=[CH2:32].[CH:34]1([NH2:37])[CH2:36][CH2:35]1.C([Mg]Cl)(C)C>C1COCC1.CN(C=O)C>[CH2:30]([N:19]1[CH:18]=[CH:17][C:16]2[C:21](=[CH:22][CH:23]=[C:14]([C:5]3[CH:6]=[C:7]([CH:12]=[CH:13][C:4]=3[CH3:3])[C:8]([NH:37][CH:34]3[CH2:36][CH2:35]3)=[O:10])[CH:15]=2)[C:20]1=[O:24])[CH:31]=[CH2:32]

Participants

9

Reactant 6

HCID 6584Methyl AcetateHCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 69828CyclopropylamineHCID 575518084-Methyl-3-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-benzoic acid, methyl ester2×HCID 178418918HCID 178418918, compound

Product 1

HCID 250204563-(2-Allyl-1-oxo-1,2-dihydro-isoquinolin-6-yl)-n-cyclopropyl-4-methyl-benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (75 mg, 60% in oil) was added to a stirred mixture of 4-methyl-3-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-benzoic acid, methyl ester (Intermediate 3) (250 mg), methyl acetate (0.5 mL) and DMF (5 mL). The mixture was stirred for 15 minutes. Allyl bromide (0.5 mL) was added via syringe and the mixture was stirred for 30 minutes, then quenched with sat. aqueous NH4Cl solution and extracted into ethyl acetate. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo to give crude ester. The ester was treated with THF (5 mL) and cyclopropylamine (0.3 mL). A solution of isopropylmagnesium chloride (2M, 0.4 mL) in THF was added dropwise. The reaction mixture was stirred for 10 minutes, quenched with sat. aqueous NH4Cl solution and extracted into ethyl acetate. The phases were separated, the organic phase was dried (Na2SO4), filtered and concentrated in vacuo to give crude product (380 mg). A sample (80 mg) of crude product was purified by HPLC to give an analytical sample of the title compound as a solid (45 mg).

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. customquenched with sat. aqueous NH4Cl solution
  3. extractionextracted into ethyl acetate
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give crude ester
  8. stirringThe reaction mixture was stirred for 10 minutes
  9. customquenched with sat. aqueous NH4Cl solution
  10. extractionextracted into ethyl acetate
  11. customThe phases were separated
  12. dry with materialthe organic phase was dried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customto give crude product (380 mg)
  16. customA sample (80 mg) of crude product was purified by HPLC

Sources & evidence

ORD record
ord-cfe049cfe1894575993f21ab7de151ea
Source dataset
uspto-grants-2011_09
Patent number
US08012979B2

Reaction notes

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