1,2-Dichloroethane → 4-[2-[1-[4-[N'-(2-fluorophenyl)ureido)-3-methoxyphenylacetyl]-2-pyrrolidinyl]ethynyl]benzoic Acid

Participants

Reaction Steps

A mixture of 4-[N′-(2-fluorophenyl)ureido]-3-methoxyphenylacetic acid (255 mg, 0.8 mmol), 2-[2-(4-ethoxycarbonylphenyl)ethynyl]pyrrolidine (195 mg, 0.8 mmol), EDC (230 mg, 1.2 mmol), DMAP (98 mg, 0.8 mmol) in DMF (20 mL) was stirred overnight. The reaction mixture was poured into 1 N HCl and the resulting precipitate was collected with suction and dissolve in CHCl3. The solution was dried over MgSO4 and evaporated. The residue was chromatographed on silica gel with CHCl3-MeOH (100:1, v/v) as eluent to give the desired compound, which was dissolved in THF (8 mL). 0.25 N NaOH (8 mL) was added to this solution and the resulting mixture was stirred overnight. The mixture was poured into 1 N HCl and extracted with CHCl3. The extract was washed with brine, dried over MgSO4, and evaporated. The residue was recrystallized from CHCl3-n-hexane to give 144 mg (37%) 33 as a pale yellow crystalline powder. mp 152–155 (d); 1H-NMR (DMSO-d6) δ 1.92–2.27 (4 H, m), 2.50 (2 H, s), 3.33–3.78 (2 H, m), 3.80 and 3.82 (total 3 H, s, each), 4.88–5.12 (1 H, m), 6.77–7.24 and 7.99–8.20 (total 7 H, m), 7.48 and 7.52 (2 H, d, J=8.3 Hz, each), 7.91 (2H, d, J=8.3 Hz), 8.72 (1H, s), 9.18 (1H, s), 13.11 (1H, br-s); MS (FAB) m/z 516 (M++1); Anal. Calcd for C29H26N3O5F.2H2O: C, 63.15; H, 5.48; N, 7.62. Found: C, 63.58; H, 5.15; N, 7.22.

Provenance & Evidence