Ether hydrochloride → n-{[2-(2,6-Dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(3-pyridylamino)carboxamide hydrochloride

HRID 10056

Reaction equation

HRID 10056 reaction equation
[ClH:1].CCOCC.[O:7]=[C:8]1[CH:13]([N:14]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][C:20]=3[CH2:24][NH:25][C:26]([NH:28][C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)=[O:27])[C:15]2=[O:35])[CH2:12][CH2:11][C:10](=[O:36])[NH:9]1>CO.C(OCC)(=O)C>[ClH:1].[O:7]=[C:8]1[CH:13]([N:14]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][C:20]=3[CH2:24][NH:25][C:26]([NH:28][C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)=[O:27])[C:15]2=[O:35])[CH2:12][CH2:11][C:10](=[O:36])[NH:9]1

Participants

5

Reactant 2

HCID 10953452Ether hydrochlorideHCID 21988574N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(3-pyridylamino)carboxamide

Product 1

HCID 21988580n-{[2-(2,6-Dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(3-pyridylamino)carboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.29 g, 1.9 mmol) was added to a stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride (0.6 g, 1.85 mmol) in acetonitrile (50 mL). After stirring for 20 min, (2,5-dioxopyrrolidinyloxy)-N-(3-pyridyl)carboxamide (0.44 g, 1.85 mmol) was added. The mixture was stirred at room temperature for 17 hours. The mixture was filtered and the solid was recrystallized from methanol (25 mL) to give N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(3-pyridylamino)carboxamide (0.23 g, 30%). 2N HCl/ether was added to a stirred solution of N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(3-pyridylamino)carboxamide (0.23 g) in methanol (5 mL) and ethyl acetate (10 mL). The mixture was stirred for 2 hours and filtered to give N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}(3-pyridylamino)carboxamide hydrochloride (0.2 g) as a white solid: mp 263–265° C.; 1H NMR (DMSO-d6) δ 11.17 (s, 1H), 10.43 (s, 1H), 9.08 (d, J=1.7 Hz, 1H), 8.44 (d, J=5.4 Hz, 1H), 8.33–8.29 (dd, J=1.2 and 8.5 Hz, 1H), 7.93–7.78 (m, 4H), 7.55 (t, J=6.0 Hz, 1H), 5.21–5.14 (dd, J=5.a and 12.5 Hz, 1H), 4.80 (d, J=5.9 Hz, 2H), 2.97–2.84 (m, 1H), 2.65–2.50 (m, 2H), 2.10–2.06 (m, 1H); 13C NMR (DMSO-d6) δ 172.78, 169.83, 167.54, 166.96, 154.78, 139.97, 139.51, 134.80, 134.37, 133.35, 132.34, 131.60, 130.43, 127.17, 127.10, 121.99, 48.88, 38.68, 30.94, 21.99; Anal. Calcd. For C20H18N5O5Cl: C, 54.12; H. 4.09; N, 15.78; Cl, 7.99. Found: C, 54.11; H, 4.10; N, 15.44; Cl, 7.81.

Workup

  1. filtrationfiltered

Sources & evidence

ORD record
ord-6dfb46c1d0d3403ba8b916c2274dc7e4
Source dataset
uspto-grants-2006_08
Patent number
US07091353B2

Linked notes

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