Water → 6-Dimethylamino-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one

HRID 2069750Notes

Reaction equation

HRID 2069750 reaction equation
[CH3:1][N:2]([CH3:48])[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([C:14]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([C:38]([N:40]5[CH2:45][CH2:44][O:43][CH2:42][CH2:41]5)=[O:39])=[CH:34][N:33]=4)[C:28](=[O:46])[N:27]([CH3:47])[CH:26]=3)[C:15]=1[CH2:16][O:17]C(=O)C)[CH:7]=[CH:6]2.O.[OH-].[Li+]>O1CCCC1.CO>[CH3:1][N:2]([CH3:48])[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([C:14]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([C:38]([N:40]5[CH2:45][CH2:44][O:43][CH2:42][CH2:41]5)=[O:39])=[CH:34][N:33]=4)[C:28](=[O:46])[N:27]([CH3:47])[CH:26]=3)[C:15]=1[CH2:16][OH:17])[CH:7]=[CH:6]2

Participants

6

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 59216499Acetic acid 2-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzyl ester

Product 1

HCID 441829386-Dimethylamino-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-oneYield 73.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To Acetic acid 2-(6-dimethylamino-1-oxo-1H-isoquinolin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzyl ester (29 mg, 0.045 mmol) in 2 ml tetrahydrofuran, 1 ml methanol, and 1 ml water was added 1M aq. lithium hydroxide solution (0.13 mL, 0.13 mmol). After stirring for 18 hours, this was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by preparative TLC (5% methanol/dichloromethane) to yield 6-Dimethylamino-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one (20 mg, 0.033 mmol). MS (ESI) 607.2 (M+H)+.

Workup

  1. customthis was partitioned between ethyl acetate and water
  2. washThe ethyl acetate layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified by preparative TLC (5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-19058dff907843038ce30484b65f1e97
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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