4-(3-HYDROXY-PROPYL)-BENZONITRILE

4) To a solution of LiBH4 (14 g, 0.65 mol) in dry ether (400 mL) was added 3- (4-cyanophenyl) propionic acid ethyl ester (50 g, 0.249 mol; see step (ii) above), followed by methanol (27 mL) dropwise. The reaction mixture was refluxed for 3h. After completion (monitored by TLC), the reaction was quenched by adding cold, saturated ammonium chloride solution (100 mL), followed by water (300 mL). The layers were then separated. The aqueous layer was extracted with ether (2 x 100 mL) and the combined organic layers were washed with brine. After drying over anhydrous sodium sulfate, the organic layer was concentrated to give the crude product. This crude product was purified by column chromatography over silica gel, using ethyl acetate in petroleum ether as eluent. This yielded 16.5 g (42percent) of the sub- title compound as a pale yellow liquid.33B 3-(4-Cyanophenyl)propan-1-ol 3-(p-Cyanophenyl)propanol (21); 4-cyanobenzaldehyde (5 g, 0.038 mol) and triphenylphosphoranylidene acetic acid ethyl ester (16 g, 0.045 mol) were dissolved in dry toluene (70 ml) and the solution was stirred at room temperature for 12 h. Then the solvent was removed under vacuum, and the residue was taken up with ether. The solid formed was removed by filtration and the organic phase was evaporated to give 3-(4-cyano-phenyl)-3-propenoic acid ethyl ester as a yellow oil. The compound was purified with flash chromatography (Hex/EtOAc). After evaporation of the desired fractions a white semi solid was obtained (6 g). The product was dissolved in ethanol and added dropwise to a suspension of sodium borohydride (11 g, 0.28 mol) in ethanol (100 ml) cooled at 0° C. The mixture was allowed to reach room temperature, and stirring was maintained for 18 h. 5 ml of acetone in 20 ml water was added dropwise to the mixture to destroy the remaining NaBH4. The solvent was evaporated and water was added. This solution was three times extracted with EtOAc. The combined organic solutions were washed twice with 2N HCl and once with brine. The organic phase was dried and subsequent evaporation of the solvent a light yellow oil. 3 g, 47percent yield.MS (ESI): m/z M+1=1601H NMR (CDCl3, 400 MHz): delta. 1.90 (m, 2H), 2.75 (t, 2H), 3.65 (t, 2H), 7.28-7.32 (m, 2H), 7.53-7.59 (m, 2H). Preparation of further compounds according to the invention.Amidine compounds 8 were synthesised as described by Powers et al. (scheme 2), but we used the procedure with Cu(OTf)2 to prepare the diphenyl phosphonate (20) (Jackson, S. D.; Fraser, S. A.; Ni, L.-M. ; Kam, C-M . ; Winkler, U. ; Johnson, D. A.; Froelich, C. J.; Hudig, D.; and Powers, J. C. Synthesis and Evaluation of Diphenyl Phosphonate Esters as Inhibitors of the Trypsin-like Granzymes A and K and Mast Cell Tryptase. J. Med. Chem., 1998, 41 , 2289-2301). Z-(4-AmPhGly)p(OPh)2 was prepared by a Lewis acid catalyzed amidoalkylation reaction, starting with cyanobenzaldehyde (18a) to give Z-(4- CN-PhGly)p(OPh)2 (20a) which was converted to the amidine (8a) using a Pinner type reaction. The 4-amidinophenylalanine phosphonate diphenyl ester derivative Z-(4- AmPhe)p(OPh)2 was synthesised in the same way from 4-cyanophenylacetaldehyde. 4- EPO

Molecular Weight:161.20
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:161.084063974
Monoisotopic Mass:161.084063974
Topological Polar Surface Area:44
Heavy Atom Count:12
Complexity:162
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes