Cyclopentanecarboxylic acid, 2-oxo-, methyl ester → 2-((3-(4-(4-methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)methyl)-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one

HRID 1752272Notes

Reaction equation

HRID 1752272 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:27]=[CH:26][C:7]([C:8]([CH:10]2[CH2:15][CH2:14][N:13]([CH:16]3[CH2:20][CH2:19][N:18]([CH2:21][C:22](=[NH:24])[NH2:23])[C:17]3=[O:25])[CH2:12][CH2:11]2)=[O:9])=[CH:6][CH:5]=1.O=[C:29]1[CH2:33][CH2:32][CH2:31][CH:30]1[C:34](OC)=[O:35].[O-]CC.[Na+]>C(O)C>[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([C:8]([CH:10]2[CH2:15][CH2:14][N:13]([CH:16]3[CH2:20][CH2:19][N:18]([CH2:21][C:22]4[NH:23][C:34](=[O:35])[C:30]5[CH2:31][CH2:32][CH2:33][C:29]=5[N:24]=4)[C:17]3=[O:25])[CH2:12][CH2:11]2)=[O:9])=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 66328Cyclopentanecarboxylic acid, 2-oxo-, methyl esterHCID 2723922Sodium ethoxideHCID 893757462-(3-(4-(4-Methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)acetimidamide hydrochloride

Product 1

HCID 1362327312-((3-(4-(4-methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)methyl)-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-oneYield 20%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-(3-(4-(4-methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)acetimidamide hydrochloride (140 mg, 0.37 mmol) and methyl 2-oxocyclopentanecarboxylate (0.060 mL, 0.47 mmol) in ethanol (4 mL) was added sodium ethoxide (0.160 mL, 0.44 mmol, 21%). The mixture was heated at 100° C. for 24 h. The resulting mixture was purified via flash column chromatography (methanol: dichloromethane, 1:99 to 10:90) and then crystalized out from methanol to provide slightly yellow solid (33 mg, 20% yield). 1H NMR (400 MHz, CDCl3) δ 10.85 (s, 1H), 7.95 (d, J=8.5 Hz, 2H), 6.96 (d, J=8.5 Hz, 2H), 4.32-4.47 (m, 2H), 3.89 (s, 3H), 3.60-3.73 (m, 1H), 3.40-3.56 (m, 2H), 3.23-3.37 (br. s, 1H), 3.00-3.20 (br. s, 3H), 2.84 (ddd, 4H, J=14.7, 7.5, 7.4 Hz), 2.46-2.62 (br. s, 1H), 2.38 (d, 1H, J=7.0 Hz), 2.15-2.25 (br. s, 1H), 2.10 (dq, 2H, J=7.8, 7.6 Hz), 1.82-2.01 (br. s, 4H) HRMS calculated for C25H30N4O4 451.2345. found (ESI, [M+H]+), 451.2362.

Workup

  1. customThe resulting mixture was purified via flash column chromatography (methanol: dichloromethane, 1:99 to 10:90)
  2. customcrystalized out from methanol

Sources & evidence

ORD record
ord-e747824ff17b43cc955a99708cb86fd5
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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