2,5-Dioxopyrrolidin-1-yl 2-cyanoacetate → HCID 59216388, compound

HRID 2245743Notes

Reaction equation

[NH2:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([C:10]2[C:11]([CH2:30][OH:31])=[C:12]([N:16]3[CH2:25][CH2:24][C:23]4[C:18](=[CH:19][CH:20]=[C:21]([N:26]([CH3:28])[CH3:27])[CH:22]=4)[C:17]3=[O:29])[CH:13]=[CH:14][CH:15]=2)[CH:3]=1.O=C1CCC(=O)N1[O:39][C:40](=O)[CH2:41][C:42]#[N:43]>O1CCOCC1.C(O)C.C(OC(=O)C)C>[C:42]([CH2:41][C:40]([NH:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([N:16]3[CH2:25][CH2:24][C:23]4[C:18](=[CH:19][CH:20]=[C:21]([N:26]([CH3:27])[CH3:28])[CH:22]=4)[C:17]3=[O:29])[C:11]=2[CH2:30][OH:31])[CH:3]=1)=[O:39])#[N:43]

Participants

Conditions

Temperature: 55 °C

Procedure

2-[3-(5-Amino-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-2-hydroxymethyl-phenyl]-6-dimethylamino-3,4-dihydro-2H-isoquinolin-1-one (40 mg, 0.095 mmol) was placed in a mixture of 1.5 ml dioxane and 0.5 ml of ethanol. To this mixture was added cyano-acetic acid 2,5-dioxo-pyrrolidin-1-yl ester, at first 1 equivalent (17.4 mg, 0.095 mmol), and then over a period of 3 days 5 more equivalents of this reagent at 2-4 hours intervals. During this time the reaction mixture was heated at 50-60° C. After cooling, the reaction mixture was diluted with ethylacetate, washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by Prep TLC with 5% methanol in dichloromethylene to afford 12 mg (26% yield) of 2-Cyano-N-{5-[3-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl}-acetamide.

Workup

temperatureAfter cooling
washwashed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by Prep TLC with 5% methanol in dichloromethylene

Sources & evidence

ORD record: ord-5a9a5c7a45e4484bbbca560aa7e09fd6
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07683064B2

Reaction notes

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