Hydrazinecarboxaldehyde → HCID 24945872, compound

HRID 751018Notes

Reaction equation

HRID 751018 reaction equation
[CH:1]1([C:4]([NH:6][C:7]2[CH:8]=[CH:9][CH:10]=[C:11]3[C:15]=2[C:14](=[O:16])[N:13]([CH:17]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=2)[CH2:18][C:19]([OH:21])=O)[CH2:12]3)=[O:5])[CH2:3][CH2:2]1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:45]([NH:47][NH2:48])=O.P(Cl)(Cl)(Cl)=O>C1COCC1.C(#N)C>[CH2:31]([O:30][C:24]1[CH:23]=[C:22]([CH:17]([N:13]2[C:14](=[O:16])[C:15]3[C:11](=[CH:10][CH:9]=[CH:8][C:7]=3[NH:6][C:4]([CH:1]3[CH2:3][CH2:2]3)=[O:5])[CH2:12]2)[CH2:18][C:19]2[O:21][CH:45]=[N:47][N:48]=2)[CH:27]=[CH:26][C:25]=1[O:28][CH3:29])[CH3:32]

Participants

7

Reactant 4

HCID 12229HydrazinecarboxaldehydeHCID 24813Phosphorus oxychlorideHCID 682631,1'-CarbonyldiimidazoleHCID 22177176HCID 22177176, compound

Product 1

HCID 24945872HCID 24945872, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

Cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-2-[1,3,4]oxadiazol-2-yl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide was prepared by reacting 3-[7-(cyclopropanecarbonyl-amino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(3-ethoxy-4-methoxy-phenyl)-propionic acid (400 mg, 0.9 mmol), CDI (160 mg, 1.0 mmol) and formic hydrazide (0.09 g, 1.5 mmol) in THF (5 mL). The crude was then reacted with phosphorus oxychloride (0.18 mL, 1.9 mmol) in acetonitrile (15 mL). The product was obtained as a white solid (60 mg, 15% yield): mp 181-183° C.; 1H NMR (CDCl3) δ 0.86-0.92 (m, 2H, cyclopropyl CH2), 1.06-1.11 (m, 2H, cyclopropyl CH2), 1.45 (t, J=7.5 Hz, 3H, CH3), 1.58-1.68 (m, 1H, cyclopropyl CH), 3.66 (dd, J=5, 15 Hz, 1H, CHH), 3.85 (dd, J=10, 15 Hz, 1H, CHH), 3.87 (s, 3H, CH3), 4.03-4.11 (m, 3H, OCH2CH3+CHH), 4.43 (d, J=17 Hz, 1H, CHH), 5.86-5.91 (m, 1H, NCH), 6.85-6.90 (m, 2H, Ar), 6.96-7.01 (m, 2H, Ar), 7.43 (t, J=7.5 Hz, 1H, Ar), 8.35 (s, 1H, Ar), 8.41 (d, J=7.5 Hz, 1H, Ar), 10.41 (s, 1H, NH); 13C NMR (CDCl3) δ 8.27, 8.29, 14.73, 16.16, 28.04, 46.36, 52.26, 55.98, 64.64, 111.53, 112.36, 116.80, 116.96, 117.80, 119.16, 129.54, 133.43, 138.06, 141.25, 148.84, 149.64, 153.34, 163.79, 169.50, 172.66. Analy. calculated for C25H25N4O5+0.1H2O: C, 64.47; H, 5.69; N, 12.07. Found: C, 64.50; H, 5.70; N, 11.69.

Sources & evidence

ORD record
ord-4f4d9825b73544d991cca18ec645e582
Source dataset
uspto-grants-2008_07
Patent number
US07405237B2

Reaction notes

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