Hydrazinecarboxaldehyde → N-carbonylamino-3-(3-ethoxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl)propanamide

HRID 2268090Notes

Reaction equation

HRID 2268090 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:17]2[C:25](=[O:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[CH3:27])[C:18]2=[O:28])[CH2:13][C:14]([OH:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:41]([NH:43][NH2:44])=[O:42]>O1CCCC1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:17]2[C:25](=[O:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[CH3:27])[C:18]2=[O:28])[CH2:13][C:14]2[O:16][CH:41]=[N:43][N:44]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[C:41](=[N:43][NH:44][C:14](=[O:15])[CH2:13][CH:12]([C:6]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)[N:17]1[C:25](=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][C:23]=2[CH3:27])[C:18]1=[O:28])=[O:42]

Participants

6

Reactant 3

HCID 12229HydrazinecarboxaldehydeHCID 682631,1'-CarbonyldiimidazoleHCID 21988665HCID 21988665, compound

Product 2

HCID 18349242HCID 18349242, compoundHCID 86757626N-carbonylamino-3-(3-ethoxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl)propanamideYield 54.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[1-(3-Ethoxy-4-methoxyphenyl)-2-(1,3,4-oxadiazol-2-yl)ethyl]-4-methylisoindoline-1,3-dione was prepared by the procedure of Example 1. Reaction of 3-(3-ethoxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl)propanoic acid (2.03 g, 5.29 mmol), carbonyldiimidazole (1.03 g, 6.35 mmol) and formic hydrazide (420 mg, 6.99 mmol) in tetrahydrofuran (20 mL) gave crude N-carbonylamino-3-(3-ethoxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl)propanamide(610 mg, 1.43 mmol), which was then treated with phosphorus oxychloride (0.4 mL, 4.3 mmol) in acetonitrile (6 mL). The product was obtained as a white solid (311 mg, 14% overall yield): mp, 96.0-98.0° C.; 1H NMR (CDCl3) δ 1.47 (t, J=6.9 Hz, 3H, CH3), 2.67 (s, 3H, CH3), 3.81 (dd, J=6.0, 15.7 Hz, 1H, CHH), 3.85 (s, 3H, CH3), 4.12 (q, J=6.9 Hz, 2H, CH2), 4.37 (dd, J=10.2, 15.6 Hz, 1H, CHH), 5.81 (t, J=6.0, 10.3 Hz, 1H, NCH), 6.83 (d, J=8.7 Hz, 1H, Ar), 7.14-7.17 (m, 2H, Ar), 7.43 (d, J=7.6 Hz, 1H, Ar), 7.54 (t, J=7.3 H, Ar), 7.63 (d, J=7.1 Hz, 1H, Ar), 8.30 (s, 1H, CH); 13C NMR (CDCl3) δ 14.69, 17.52, 27.71, 51.62, 55.92, 64.46, 111.37, 112.63, 120.33, 121.06, 128.31, 130.33, 132.07, 133.59, 136.55, 138.18, 148.39, 149.42, 153.02, 164.08, 168.04, 168.53; Anal Calcd for C22H21N3O5+0.2 H2O: C, 64.29; H, 5.25; N, 10.22; H2O, 0.90. Found: C, 64.62; H, 5.30; N, 9.83; H2O, 0.71.

Sources & evidence

ORD record
ord-d4c9d2022dc943fe97fc03c054f67d51
Source dataset
uspto-grants-2001_12
Patent number
US06326388B1

Reaction notes

Loading…