Dimethyl Sulfoxide → 4-[(3,4-Dimethylphenyl)(methyl)amino]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinecarbaldehyde

HRID 572518Notes

Reaction equation

HRID 572518 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C:12]1[CH:13]=[C:14]([N:19]([CH3:34])[C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23](=[O:30])[N:22]([CH3:31])[C:21]=2[CH2:32][OH:33])[CH:15]=[CH:16][C:17]=1[CH3:18].CCN(CC)CC>C(Cl)Cl>[CH3:11][C:12]1[CH:13]=[C:14]([N:19]([CH3:34])[C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23](=[O:30])[N:22]([CH3:31])[C:21]=2[CH:32]=[O:33])[CH:15]=[CH:16][C:17]=1[CH3:18]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 683528484-[(3,4-Dimethylphenyl)(methyl)amino]-3-(hydroxymethyl)-2-methyl-1(2H)-isoquinolinone

Product 1

HCID 867007224-[(3,4-Dimethylphenyl)(methyl)amino]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinecarbaldehydeYield 67.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of oxalyl chloride (0.015 mL, 0.172 mmol) in DCM (5 mL) at −70° C. was added dropwise DMSO (0.024 mL, 0.344 mmol). After 15 min a solution of 4-[(3,4-dimethylphenyl)(methyl)amino]-3-(hydroxymethyl)-2-methyl-1(2H)-isoquinolinone (25 mg, 0.078 mmol) in DCM (1 mL) was added slowly, and the mixture was kept at −78° C. for 30 min. Then NEt3 (38 uL) was added and the reaction was kept at −78° C. for 1 hour. The mixture was quenched with aq. NaHCO3 and extracted with dichloromethane. The organic phase was dried over sodium sulfate and evaporated to give the crude title compound as yellow oil (16.9 mg, 61.4%). 1H NMR (400 MHz, CDCl3) δ ppm 9.97-9.78 (m, 1 H), 8.64-8.46 (m, 1 H), 7.75-7.54 (m, 2 H), 7.51-7.42 (m, 1 H), 7.07-6.92 (m, 1 H), 6.59-6.38 (m, 2 H), 3.87 (s, 3 H), 3.40 (s, 3 H), 2.18 (d, J=6.3 Hz, 6 H); ES-LCMS: 321.1 (M+1).

Workup

  1. waitthe reaction was kept at −78° C. for 1 hour
  2. customThe mixture was quenched with aq. NaHCO3
  3. extractionextracted with dichloromethane
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. customevaporated

Sources & evidence

ORD record
ord-4d06197666ce480fb8e6fc0c30fba5db
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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