[C:1]([OH:13])(=O)[CH2:2][NH:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].C1CCC([N:20]=[C:21]=[N:22]C2CCCCC2)CC1.ON1C(=O)CCC1=O.N#CN.[Na]>C(#N)C.O.CCOC(C)=O.CC(O)=O>[C:4]([NH:3][CH2:2][C:1]([NH:22][C:21]#[N:20])=[O:13])(=[O:5])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Hippuric acid (3.58 g, 0.020 mol), DCC (4.13 g, 0.020 mol), and N-hydroxysuccinimide (2.3 g, 0.020 mol) were stirred in 100 ml of acetonitrile at ice bath temperature for 2 hours. The reaction mixture was filtered to remove the bulk of by-product DCU. The filtrate was evaporated in vacuo to dryness, the residue was redissolved in THF and the mixture was filtered to remove any residual DCU. The filtrate (70 ml) was added drop-wise to a solution of sodium cyanamide (3.84 g, 0.060 mol) in 100 ml of distilled water with vigorous stirring at ice bath temperature. The reaction was allowed to proceed at room temperature overnight. The reaction mixture (pH 11) was extracted with ethyl acetate (2×60 ml) and the separated aqueous layer was acidified to pH 1.5 with 10% HCl. The resulting solid suspension was filtered to give 2.28 g (56.1% yield) of white crystalline 10. It was recrystallized from THF/acetonitrile/petroleum ether to yield 0.78 g (crop 1) of white crystalline product. The filtrate was concentrated to yield 0.9 g (crop 2) of additional crystals. Mp dec. > 155° C. (turns to brown oil at 160° C.); TLC: Rf =0.36 in EtOAc/AcOH (100:1), detected by UV quenching and orange color with ferricyanide spray reagent; IR (Nujol, cm-1) 3400 (NH), 3080 (C6H5), 2220 (C≡N), 1710 and 1620 (C=O); NMR (Silanor C and DMSO (1:1), δ from TMS) 8.2-8.4 (broad, NH); 7.3-8.0 (m, C6H5 --), 4.1-4.2 (d, --NH--CH2 --CO). Anal. Calcd for C10H9N3O2 : C, 59.11; H, 4.46; N, 20.68. Found: C, 59.26; H, 4.46; N, 20.84 (crop 1) and C, 59.03; H, 4.20; N, 20.80 (crop 2).
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