Hydrazinecarboxaldehyde → HCID 10141202, compound

HRID 2268094Notes

Reaction equation

HRID 2268094 reaction equation
[C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:34])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)[CH:21]=1)[CH2:16][C:17]([OH:19])=[O:18])[C:9]2=[O:14])(=[O:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:47]([NH:49][NH2:50])=[O:48]>C(OCC)(=O)C>[CH:29]1([O:28][C:22]2[CH:21]=[C:20]([CH:15]([N:8]3[C:7](=[O:34])[C:6]4[C:10](=[CH:11][CH:12]=[CH:13][C:5]=4[NH:4][C:1](=[O:3])[CH3:2])[C:9]3=[O:14])[CH2:16][C:17]3[O:18][CH:47]=[N:49][N:50]=3)[CH:25]=[CH:24][C:23]=2[O:26][CH3:27])[CH2:30][CH2:31][CH2:32][CH2:33]1.[C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:34])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH:29]3[CH2:30][CH2:31][CH2:32][CH2:33]3)[CH:21]=1)[CH2:16][C:17]([NH:50][N:49]=[C:47]=[O:48])=[O:19])[C:9]2=[O:14])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 12229HydrazinecarboxaldehydeHCID 682631,1'-CarbonyldiimidazoleHCID 21988663HCID 21988663, compound

Product 2

HCID 10141202HCID 10141202, compoundHCID 86757630HCID 86757630, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

N-[2-[1-(3-Cyclopentyloxy-4-methoxyphenyl)-2-(1,3,4-oxadiazol-2-yl)ethyl]-1,3-dioxoisoindolin-4-yl]acetamide was prepared by the procedure of Example 1. Reaction of 3-[4-(acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-cyclopentyloxy-4-methoxyphenyl)propanoic acid (2.0 g, 4.3 mmol), carbonyidiimidazole (0.77 g, 4.8 mmol) and formic hydrazide (314 mg, 4.7 mmol) in ethyl acetate (20 mL) gave crude 3-[4-(acetylamino)-1,3-dioxoisoindolin-2-yl]-N-carbonylamino-3-(3-cyclopentyloxy-4-methoxyphenyl)propanamide, which was then reacted with phosphorus oxychloride (1.0 mL, 10.7 mmol) in acetonitrile (15 mL). The product was isolated as a yellow solid (555 mg, 28% overall yield): mp, 115.0-117.0° C.; 1H NMR (CDCl3) δ 1.62-1.97 (m, 8H, C5H8), 2.27 (s, 3H, CH3), 3.76 (dd, J=5.6, 15.9 Hz, 1H, CHH), 3.83 (s, 3H, CH3), 4.40 (dd, J=10.7, 15.8 Hz, 1H, CHH), 4.76-4.82 (m, 1H, OCH), 5.78 (dd, J=5.5, 10.7 Hz, 1H, NCH), 6.84 (d, J=8.1 Hz, 1H, Ar), 7.09-7.15 (m, 2H, Ar), 7.47 (d, J=7.2 Hz, 1H, Ar), 7.65 (t, J=7.5 Hz, 1H, Ar), 8.32 (s, 1H, CH), 8.76 (d, J=8.4 Hz, 1H, Ar), 9.48 (s, 1H, NH); 13C NMR (CDCl3) δ 23.99, 24.85, 27.58, 32.68, 51.71, 55.95, 80.53, 111.75, 114.46, 115.10, 118.03, 119.88, 124.82, 129.77, 130.95, 135.94, 137.48, 147.77, 150.21, 152.99, 163.85, 167.36, 169.07, 167.71; Anal Calcd for C26H26N4O6+0.1 hexane: C, 64.01; H, 5.53; N, 11.22. Found: C, 64.01; H, 5.58; N, 10.97. (HNMR showed the product contained 10% of hexane).

Sources & evidence

ORD record
ord-0d83bfb34abf492e89e22f4ad9616871
Source dataset
uspto-grants-2001_12
Patent number
US06326388B1

Reaction notes

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