Methanol → 2-(4-((cyclopropylamino)methyl)pyridin-3-yl)-7-(trifluoromethyl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 1843973Notes

Reaction equation

HRID 1843973 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[O:5]=[C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=2)[CH2:9][CH2:8][N:7]1[C:20]1[CH:27]=[N:26][CH:25]=[CH:24][C:21]=1[CH:22]=O.CO.C([O-])(O)=O.[Na+]>C(O)(=O)C.C(Cl)(Cl)Cl>[CH:1]1([NH:4][CH2:22][C:21]2[CH:24]=[CH:25][N:26]=[CH:27][C:20]=2[N:7]2[CH2:8][CH2:9][C:10]3[C:15](=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=3)[C:6]2=[O:5])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 887MethanolHCID 69828CyclopropylamineHCID 516892Sodium BicarbonateHCID 871589583-(1-oxo-7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl) isonicotinaldehyde

Product 1

HCID 569430522-(4-((cyclopropylamino)methyl)pyridin-3-yl)-7-(trifluoromethyl)-3,4-dihydroisoquinolin-1(2H)-oneYield 22.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6212ChloroformSolvent

Procedure

Cyclopropanamine (25.8 μL, 0.3737 mmol) was added to a stirred solution of 3-(1-oxo-7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl)isonicotinaldehyde (I-53c: 100 mg, 0.3114 mmol) in acetic acid (5 mL) and resulting reaction mixture was stirred for 4 hours at room temperature. The reaction mass was cooled to 0° C. and added NaBH(OCH3)3 (99 mg, 0.4674 mmol). The resulting reaction mass was stirred for 12 hours at room temperature. The reaction was monitored by TLC (10% methanol in CHCl3). The reaction mass was concentrated under reduced pressure, the crude residue obtained was diluted with ice, basified using saturated NaHCO3 solution to pH 7 and extracted using CHCl3. The organic layer was washed with water, brine solution, dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography on silica gel (2% methanol in CHCl3) afforded 25 mg of the product (22% yield).

Workup

  1. customresulting
  2. customreaction mixture
  3. temperatureThe reaction mass was cooled to 0° C.
  4. customThe resulting reaction mass
  5. stirringwas stirred for 12 hours at room temperature
  6. concentrationThe reaction mass was concentrated under reduced pressure
  7. customthe crude residue obtained
  8. additionwas diluted with ice
  9. extractionextracted
  10. washThe organic layer was washed with water, brine solution
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated under reduced pressure
  13. customPurification by column chromatography on silica gel (2% methanol in CHCl3)

Sources & evidence

ORD record
ord-74dc0a455fd54c3894e2daf570011758
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

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