Methyl 4-[(3,4-dimethylphenyl)(methyl)amino]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate → 4-[(3,4-Dimethylphenyl)(methyl)amino]-3-(hydroxymethyl)-2-methyl-1(2H)-isoquinolinone

HRID 572517Notes

Reaction equation

[CH3:1][C:2]1[CH:3]=[C:4]([N:9]([CH3:26])[C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[N:12]([CH3:21])[C:11]=2[C:22](OC)=[O:23])[CH:5]=[CH:6][C:7]=1[CH3:8].[BH4-].[Li+].C1COCC1>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[C:4]([N:9]([CH3:26])[C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[N:12]([CH3:21])[C:11]=2[CH2:22][OH:23])[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of methyl 4-[(3,4-dimethylphenyl)(methyl)amino]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (2.11 g, 6.02 mmol) in toluene (12 mL) was added dropwise 2 M lithium borohydride/THF (3.06 mL, 6.11 mmol). The mixture was stirred at 70° C. for 6 hours, quenched with 1M HCl/water and partitioned between EtOAc and aq. NaHCO3. The organic phase was dried over sodium sulfate, evaporated in vacuo and purified on silica using EtOAc/hexanes 20-50% to provide the title compound as an off-white solid (0.94 g, 48%). 1H NMR (400 MHz, CDCl3) δ ppm 8.51 (br. s., 1 H), 7.57 (br. s., 2 H), 6.96 (br. s., 1 H), 6.44 (br. s., 2 H), 4.80-4.48 (m, 2 H), 3.80 (br. s., 3 H), 3.27 (br. s., 3 H), 2.16 (d, 11 H), 2.29-2.06 (m, 6 H); ES-LCMS: 323.4 (M+1); ES-LCMS: 323.4 (M+1).

Workup

customquenched with 1M HCl/water
custompartitioned between EtOAc and aq. NaHCO3
dry with materialThe organic phase was dried over sodium sulfate
customevaporated in vacuo
custompurified on silica

Sources & evidence

ORD record: ord-4da69e6173914f02853134693d8d50fd
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029391B2

Reaction notes

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