1,8-Diazabicyclo(5.4.0)undec-7-ene → N-[2-(2,6-Dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide

HRID 906697

Reaction equation

N12CCCN=C1CCCCC2.CO[C:14](=[O:30])[C:15]1[C:16](=[C:21]([CH2:25][NH:26][C:27](=[O:29])[CH3:28])[CH:22]=[CH:23][CH:24]=1)[C:17]([O:19]C)=O.Cl.[NH2:32][CH:33]1[CH2:39][CH2:38][C:37](=[O:40])[NH:36][C:34]1=[O:35]>CN(C=O)C>[O:35]=[C:34]1[CH:33]([N:32]2[C:17](=[O:19])[C:16]3[C:15](=[CH:24][CH:23]=[CH:22][C:21]=3[CH2:25][NH:26][C:27](=[O:29])[CH3:28])[C:14]2=[O:30])[CH2:39][CH2:38][C:37](=[O:40])[NH:36]1

Participants

Conditions

Temperature: 120 °C

Procedure

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.93 g, 6 mmol) was added dropwise to a stirred suspension of 3-(acetylamino-methyl)-phthalic acid dimethyl ester (1.61 g, 6.0 mmol) and aminoglutarimide hydrochloride (1.0 g, 6.0 mmol) in DMF (15 ml). The mixture was then heated to 120° C. for 24 hours. The cooled mixture was concentrated in vacuo and the residue was stirred with water (25 ml) and dichloromethane (20 ml). The resulting slurry was filtered to give 0.45 g (22%) of the product as a gray solid. Recrystallization from methanol gave a white solid: mp 177-179° C.; 1H NMR (DMSO-d6) δ (11.02 (s, 1H), 8.36 (t, J=5.8 Hz, 1H), 7.74-7.55 (m, 3H), 5.05-4.98 (dd, J=5.3 and 12.5 Hz, 1H), 4.57 9D, j=5.9 Hz, 2H), 2.84-2.70 (m, 1H), 2.51-2.34 (m, 2H), 1.95-1.91 (m, 1H), 1.79 (s, 3H); 13C NMR (DMSO-d6) δ (172.85, 169.89, 169.81, 167.56, 167.05, 139.37, 134.83, 133.35, 131.58, 127.14, 121.94, 48.91, 37,84, 30.98, 22.54, 22.05; Anal. Calcd. For C16H15N3O5+0.96 water: C, 55.45; H, 4.92; N, 12.12. Found: C, 55.27; H, 4.82; N, 12.00.

Workup

concentrationThe cooled mixture was concentrated in vacuo
filtrationThe resulting slurry was filtered

Sources & evidence

ORD record: ord-2b499c6255ec43969404aa5e3a4400bc
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012997B2

Linked notes

Loading…