Hydrazinecarboxaldehyde → HCID 18349239, compound

HRID 2268095Notes

Reaction equation

HRID 2268095 reaction equation
[C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:31])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH2:29][CH3:30])[CH:21]=1)[CH2:16][C:17]([OH:19])=O)[C:9]2=[O:14])(=[O:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:44]([NH:46][NH2:47])=O.P(Cl)(Cl)(Cl)=O>C(#N)C.CCOCC.O>[CH2:29]([O:28][C:22]1[CH:21]=[C:20]([CH:15]([N:8]2[C:7](=[O:31])[C:6]3[C:10](=[CH:11][CH:12]=[CH:13][C:5]=3[NH:4][C:1](=[O:3])[CH3:2])[C:9]2=[O:14])[CH2:16][C:17]2[O:19][CH:44]=[N:46][N:47]=2)[CH:25]=[CH:24][C:23]=1[O:26][CH3:27])[CH3:30]

Participants

8

Reactant 4

HCID 12229HydrazinecarboxaldehydeHCID 24813Phosphorus oxychlorideHCID 682631,1'-CarbonyldiimidazoleHCID 21988659HCID 21988659, compound

Product 1

HCID 18349239HCID 18349239, compoundYield 27%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-[4-(acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-ethoxy-4-methoxyphenyl)propanoic acid (1.69 g, 3.96 mmol) and carbonyidiimidazole (0.71 g, 4.4 mmol) in acetonitrile (20 mL) was stirred at room temperature for 2 hours. To the solution was added formic hydrazide (289 mg, 4.81 mmol). The mixture was then stirred for 18 hours. To the resulting solution was added phosphorus oxychloride (1.0 mL, 10.7 mmol), and this mixture was heated at reflux for 2 hours. The solution was poured to water (10 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with aqueous sodium hydrogen carbonate (50 mL, sat), brine (50 mL) and then dried over magnesium sulfate. Chromatography followed by removal of solvent yielded an oil. The oil was stirred in ether (10 mL) to give a suspension. This suspension was filtered to yield N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-(1,3,4-oxadiazol-2-yl)ethyl]-1,3-dioxoisoindolin-4-yl]acetamide as a white solid (478 mg, 27% yield): mp, 141.0-143.0° C.; 1H NMR (CDCl3) δ 1.47 (t, J=6.9 Hz, 3H, CH3), 2.26 (s, 3H, CH3), 3.74 (dd, J=5.8, 15.8 Hz, 1H, CHH), 3.85 (s, 3H, CH3), 4.11 (q, J=7.1 Hz, 2H, CH2), 4.38 (dd, J=10.6, 15.8 Hz, 1H, CHH), 5.78 (dd, J=5.6, 10.6 Hz, 1H, NCH), 6.83 (d, J=8.9 Hz, 1H, Ar), 7.11-7.14 (m, 2H, Ar), 7.45 (d, J=7.2 Hz, 1H, Ar), 7.64 (d, J=7.5 Hz, 1H, Ar), 8.31 (s, 1H, Ar), 8.75 (d, J=8.4 Hz, 1H, Ar), 9.46 (br s, 1H, NH); 13C NMR (CDCl3) δ 14,70, 24.92, 27.60, 51.74, 55.92, 64.50, 111.40, 112.47, 115.15, 118.11, 120.15, 124.91, 129.87, 130.99, 136.01, 137.55, 148.49, 149.59, 153.07, 163.88, 167.44, 169.14, 169.75; Anal Calcd for C23H22N4O6: C, 61.33; H, 4.92; N, 12.44. Found: C, 61.37; H, 4.88; N, 12.11.

Workup

  1. stirringThe mixture was then stirred for 18 hours
  2. temperaturethis mixture was heated
  3. temperatureat reflux for 2 hours
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  5. washThe combined organic layers were washed with aqueous sodium hydrogen carbonate (50 mL, sat), brine (50 mL)
  6. dry with materialdried over magnesium sulfate
  7. customChromatography followed by removal of solvent
  8. customyielded an oil
  9. customto give a suspension
  10. filtrationThis suspension was filtered

Sources & evidence

ORD record
ord-8747f2fd1baf4610a99b79c0b1431199
Source dataset
uspto-grants-2001_12
Patent number
US06326388B1

Reaction notes

Loading…