Acetohydrazide → HCID 86757631, compound

HRID 2268099Notes

Reaction equation

HRID 2268099 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:17]2[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]2=[O:26])[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.[C:39]([NH:42][NH2:43])(=[O:41])[CH3:40]>O1CCCC1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:17]2[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]2=[O:26])[CH2:13][C:14]2[O:16][C:39]([CH3:40])=[N:42][N:43]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[C:39](=[N:42][NH:43][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[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]1=[O:26])=[O:41]

Participants

6

Reactant 3

HCID 14039AcetohydrazideHCID 682631,1'-CarbonyldiimidazoleHCID 183492403-(3-Ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolinyl)propanoic acid

Product 2

HCID 18349245HCID 18349245, compoundHCID 86757631HCID 86757631, compoundYield 145%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[1-(3-Ethoxy-4-methoxyphenyl)-2-(5-methyl(1,3,4-oxadiazol-2-yl))ethyl]isoindolin-1-one was prepared by the procedure of Example 1. Reaction 3-(3-ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolin-2-yl)propanoic acid (1.50 g, 4.22 mmol), carbonyldiimidazole (0.76 g, 4.7 mmol) and acetic hydrazide (381 mg, 5.16 mmol) in tetrahydrofuran (15 mL) gave crude N-carbonylamino-3-(3-ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolin-2-yl)propanamide (1.22 9, 3.06 mmol), which (650 mg, 1.47 mmol) was then reacted with phosphorus pentoxide (2.0 g, 14 mmol) in chloroform (30 mL) at room temperature for 18 hours The product was obtained as a white solid (250 mg, 32% overall yield): mp, 125.5-128.0° C.; 1H NMR (CDCl3); δ 1.43 (t, J=7.0 Hz, 3H, CH3), 2.46 (s, 3H, CH3), 3.56 (dd, J=6.3, 15.1 Hz, 1H, CHH), 3.76 (dd, J=10.0, 15.0 Hz, 1H, CHH), 3.86 (s, 3H, CH3), 4.02-4.11 (m, 3H, NCHH, CH2), 4.46 (d, J=16.6 Hz, 1H, NCHH), 5.97 (dd, J=6.3, 9.9 Hz, 1H, NCH), 6.83-6.87 (m, 1H, Ar), 6.95-7.01 (m, 2H, Ar), 7.35-7.53 (m, 3H, Ar), 7.77-7.81 (m, 1H, Ar); 13C NMR (CDCl3) δ 10.89, 14.64, 28.04, 46.18, 52.08, 55.89, 64.47, 111.32, 112.51, 119.03, 122.81, 123.74, 127.95, 130.13, 131.48, 132.11, 141.17, 148.64, 149.31, 163.86, 164.23, 168.30; Anal Calcd for C22H23N3O4+0.28 EtOAc: C, 66.42; H, 6.08; N, 10.05. Found: C, 66.47; H, 5.98; N, 10.04. (1H NMR showed that the sample contained 28% of ethyl acetate).

Sources & evidence

ORD record
ord-b5771801acba462a9473fef82a193b44
Source dataset
uspto-grants-2001_12
Patent number
US06326388B1

Reaction notes

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