2-Thiophenecarbonyl chloride → N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}-2-thienylcarboxamide

HRID 2103478Notes

Reaction equation

HRID 2103478 reaction equation
N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17](=[O:33])[N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].[S:34]1[CH:38]=[CH:37][CH:36]=[C:35]1[C:39](Cl)=[O:40]>CC#N>[O:32]=[C:26]1[CH:25]([N:18]2[C:17](=[O:33])[C:16]3[C:20](=[CH:21][CH:22]=[CH:23][C:15]=3[CH2:14][NH:13][C:39]([C:35]3[S:34][CH:38]=[CH:37][CH:36]=3)=[O:40])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

Participants

5

Reactant 3

HCID 789282-Thiophenecarbonyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 10157634N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}-2-thienylcarboxamideYield 47.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.620 g, 4.07 mmol) was added to a stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione hydrochloride (0.600 g, 1.85 mmol) in CH3CN (50 ml). After stirring for 20 min, 2-thiophene-carbonyl chloride (0.3 g, 2.03 mmol) was added. The mixture was stirred at room temperature for 17 hours. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (70 ml). The CH2Cl2 solution was washed with 1N HCl (30 ml), H2O (30 ml), brine (30 ml) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by chromatography (SiO2, CH2Cl2:EtOAc 6:4) to give N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}-2-thienylcarboxamide (0.35 g, 47%) as a white solid: mp 192-194° C.; 1H NMR (DMSO-d6) δ d 11.16 (s, 1H), 9.18 (t, J=5.8 Hz, 1H), 7.88-7.72 (m 5H), 7.20-7.17 (dd, J=3.9 and 4.7 Hz, 1H), 5.22-5.15 (dd, J=5.5 and 12.7 Hz, 1H), 4.94 (d, J=5.8 Hz, 2H), 2.98-2.85 (m, 1H), 2.66-2.50 (m, 2H), 2.11-2.06 (m, 1H); 13C NMR (DMSO-d6) δ d 172.72, 169.80, 167.51, 166.93, 161.52, 139.26, 139.14, 134.83, 133.14, 131.53, 131.11, 128.51, 127.96, 127.12, 121.93, 48.89, 38.09, 30.93, 21.99; Anal. Calcd. For C19H15N3O5S: C, 57.42; H, 3.80; N, 10.57. S, 8.07. Found: C, 57.80; H, 3.93; N, 10.22; S, 7.99.

Workup

  1. stirringThe mixture was stirred at room temperature for 17 hours
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in CH2Cl2 (70 ml)
  4. washThe CH2Cl2 solution was washed with 1N HCl (30 ml), H2O (30 ml), brine (30 ml)
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed in vacuo
  7. customthe residue was purified by chromatography (SiO2, CH2Cl2:EtOAc 6:4)

Sources & evidence

ORD record
ord-9f2ab6121c144d4fb0c1c57b2107b925
Source dataset
uspto-grants-2009_08
Patent number
US07576104B2

Reaction notes

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