Dimethylformamide → HCID 86723767, compound

HRID 577537Notes

Reaction equation

HRID 577537 reaction equation
[CH3:1][C:2]1[C:3]([O:19][CH:20]([CH3:22])[CH3:21])=[CH:4][C:5]([C:13]2[CH:14]=[N:15][N:16]([CH3:18])[CH:17]=2)=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.[H-].[Na+].Cl[CH2:26][C:27]1[C:32]([CH3:33])=[CH:31][C:30](C)=[CH:29][C:28]=1[O:35][CH2:36][C:37]1[C:42](C2(OCC3C=CC=CC=3)C=C(C)C=C(C)C2CCl)=[CH:41][CH:40]=[CH:39][CH:38]=1.C[N:62](C=O)C>>[CH2:36]([O:35][C:28]1[C:27]([CH2:26][N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[C:2]([CH3:1])[C:3]([O:19][CH:20]([CH3:22])[CH3:21])=[CH:4][C:5]=3[C:13]3[CH:14]=[N:15][N:16]([CH3:18])[CH:17]=3)[C:10]2=[O:12])=[C:32]([CH3:33])[CH:31]=[C:30]([CH3:29])[N:62]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 86723740HCID 86723740, compoundHCID 86723766HCID 86723766, compound

Product 1

HCID 86723767HCID 86723767, compoundYield 38%

Procedure

To a stirred solution of 8-methyl-5-(1-methyl-1H-pyrazol-4-yl)-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one (108j, 60 mg, 0.2 mmol) in DMF (5 mL) was added NaH (9.6 mg, 0.4 mmol, 60% in oil) at 0° C. under N2. After 30 minutes, 1-(benzyloxy)-2-(chloromethyl)-3,5-dimethylbenzene benzyl 2-(chloromethyl)-3,5-dimethylphenyl ether (Cpd Z, 115 mg, 0.44 mmol) was added and stirred at room temperature for 14 hours. The reaction mixture was poured into ice-water (20 mL), then extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine (2×10 mL), dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc=1:1) to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-methyl-5-(1-methyl-1H-pyrazol-4-yl)-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one (108k, 40 mg, 38%) as a white solid.

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. washThe combined organic layers were washed with brine (2×10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by column chromatography (petroleum ether/EtOAc=1:1)

Sources & evidence

ORD record
ord-4cc9c6a1065f4b8aa50872b866dce775
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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