Acetic Acid → methyl 1-oxo-2-(2-{[3-(1H-pyrazol-1-yl)phenyl]amino}ethyl)-1,2-dihydroisoquinoline-7-carboxylate

HRID 1616173Notes

Reaction equation

HRID 1616173 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[CH:5]=[CH:4][N:3]1[CH2:16][CH:17]=O.[N:19]1([C:24]2[CH:25]=[C:26]([CH:28]=[CH:29][CH:30]=2)[NH2:27])[CH:23]=[CH:22][CH:21]=[N:20]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO.O>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[CH:5]=[CH:4][N:3]1[CH2:16][CH2:17][NH:27][C:26]1[CH:28]=[CH:29][CH:30]=[C:24]([N:19]2[CH:23]=[CH:22][CH:21]=[N:20]2)[CH:25]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 216697133-(1H-pyrazol-1-yl)anilineHCID 86664205Methyl 1-oxo-2-(2-oxoethyl)-1,2-dihydroisoquinoline-7-carboxylate

Product 1

HCID 67283555methyl 1-oxo-2-(2-{[3-(1H-pyrazol-1-yl)phenyl]amino}ethyl)-1,2-dihydroisoquinoline-7-carboxylateYield 59.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of methyl 1-oxo-2-(2-oxoethyl)-1,2-dihydroisoquinoline-7-carboxylate (0.15 g, 0.61 mmol) and 3-(1H-pyrazol-1-yl)aniline (0.15 g, 0.92 mmol) in methanol (2 mL) was stirred at rt for 30 mins. Then acetic acid (3.5 μL, 0.06 mmol) and sodium cyanoborohydride (96 mg, 1.5 mmol) was added and the reaction mixture was stirred at rt overnight. The mixture was diluted with water and extracted with DCM (2×). The combined organic phases were then washed with water, and brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash silica gel chromatography (20% to 70% EtOAc/hexanes) to afford methyl 1-oxo-2-(2-{[3-(1H-pyrazol-1-yl)phenyl]amino}ethyl)-1,2-dihydroisoquinoline-7-carboxylate (0.14 g, 59%). LC-MS: (FA) ES+ 389.

Workup

  1. extractionextracted with DCM (2×)
  2. washThe combined organic phases were then washed with water, and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash silica gel chromatography (20% to 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f3c58ada8381441a9e6b9d5451bda787
Source dataset
uspto-grants-2014_07
Patent number
US08765773B2

Reaction notes

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