Hydrazinecarboxaldehyde → HCID 87483168, compound

HRID 2268087Notes

Reaction equation

HRID 2268087 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH2:26][CH3:27])[CH:18]=1)[CH2:13][C:14](O)=[O:15].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:40]([NH:42][NH2:43])=[O:41]>O1CCCC1>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH:12]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH2:26][CH3:27])[CH:18]=1)[CH2:13][C:14]([NH:43][N:42]=[C:40]=[O:41])=[O:15]

Participants

5

Reactant 3

HCID 12229HydrazinecarboxaldehydeHCID 682631,1'-CarbonyldiimidazoleHCID 120171083-(3-Ethoxy-4-methoxyphenyl)-3-phthalimidopropanoic acid

Product 1

HCID 87483168HCID 87483168, compoundYield 39.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoic acid (3.0 g, 8.1 mmol) and carbonyidiimidazole (1.45 g, 8.94 mmol) in tetrahydrofuran (15 mL) was stirred at room temperature for 2 hours. To the solution was added formic hydrazide (644 mg, 10.7 mmol). The mixture was stirred for 18 hours. The resulting suspension was filtered and washed with ether. The isolated solid was stirred in a mixture of ethyl acetate (40 mL) and water (10 mL) for 1 hour. The suspension was filtered and washed with water and ether to give crude 3-(1,3-dioxoisoindolin-2-yl)-N-carbonylamino-3-(3-ethoxy-4-methoxyphenyl)propanamide (1.3 g, 39% yield). A solution of 3-(1,3-dioxoisoindolin-2-yl)-N-carbonylamino-3-(3-ethoxy-4-methoxyphenyl)propanamide (600 mg, 1.46 mmol) and phosphorus oxychloride (POCl3, 0.54 mL, 5.8 mmol) in acetonitrile (20 mL) was heated to reflux for 2 hours. This solution was poured into water (10 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with sodium hydrogen carbonate (50 mL, sat), brine (50 mL) and dried over magnesium sulfate. Removal of solvent and chromatography gave an oil. The oil was slurried in ether (10 mL). The resulting suspension was filtered to yield 2-[1-(3-ethoxy-4-methoxyphenyl)-2-(1,3,4-oxadiazol-2-yl)ethyl]isoindoline-1,3-dione as a white solid (250 mg, 43% yield): mp, 132.0-134.0° C.; 1H NMR (CDCl3); δ 1.46 (t, J=6.9 Hz, 3H, CH3), 2.82 (dd, J=6.0, 15.6 Hz, 1H, CHH), 3.84 (s, 3H, CH3), 4.11 (q, J=7.0 Hz, 2H, CH2), 4.37 (dd, J=10.3, 15.7 Hz, 1H, CHH), 5.81 (dd, J=6.0, 10.3 Hz, 1H, NCH), 6.62 (d, J=7.9 Hz, 1H, Ar), 7.13-7.17 (m, 2H, Ar), 7.67-7.72 (m, 2H, Ar), 7.75-7.62 (m, 2H, Ar), 8.29 (s, 1H, Ar); 13C NMR (CDCl3)δ 14.69, 27.70, 51.85, 55.90, 64.42, 111.32, 112.51, 120.32, 123.44, 130.14, 13163, 134.13, 148.39, 143.43, 153.03, 163.99, 167.93; Anal Calcd for C21H29N3O5: C, 64.12; H, 4.87; N, 10.68. Found: C, 63.84; H, 4.90; N, 10.48.

Workup

  1. stirringThe mixture was stirred for 18 hours
  2. filtrationThe resulting suspension was filtered
  3. washwashed with ether
  4. stirringThe isolated solid was stirred in a mixture of ethyl acetate (40 mL) and water (10 mL) for 1 hour
  5. filtrationThe suspension was filtered
  6. washwashed with water and ether

Sources & evidence

ORD record
ord-3c0c67a559dd4b4eb731b543bff7cef5
Source dataset
uspto-grants-2001_12
Patent number
US06326388B1

Reaction notes

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