Reacción #10171

Ecuación de reacción

methyl 3,3′-difluoro-4′-({[(1-{[methoxy(oxo)acetyl]-amino}cyclopropyl)carbonyl]amino}methyl)-1,1′-biphenyl-2-carboxylate

Methyl 3,3′-difluoro-4′-({[(1-{[methoxy(oxo)acetyl]amino}cyclopropyl)-carbonyl]amino}methyl)-1,1′-biphenyl-2-carboxylate

ammonia

→

title compound

Methyl 4′-({[(1-{[amino(oxo)acetyl]amino}cyclopropyl)carbonyl]amino}methyl)-3,3′-difluoro-1,1′-biphenyl-2-carboxylate

Disolventes

methylene chloride

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónconcentrated
2. 2
   Otroto obtain the crude product
3. 3
   OtroThis crude product was purified by reverse phase HPLC (Vydac column #218TP1022, gradient elution 5–95% acetonitrile:water containing 0.1% TFA)

Procedimiento

To a solution of methyl 3,3′-difluoro-4′-({[(1-{[methoxy(oxo)acetyl]-amino}cyclopropyl)carbonyl]amino}methyl)-1,1′-biphenyl-2-carboxylate (0.02 g, 0.045 mmol, Example 5) in methylene chloride (2 mL) at room temperature was added ammonia (0.224 mL of a 2M solution in methanol, 0.45 mmol). The reaction mixture was stirred at room temperature for 4 hrs and then concentrated to obtain the crude product. This crude product was purified by reverse phase HPLC (Vydac column #218TP1022, gradient elution 5–95% acetonitrile:water containing 0.1% TFA). The pure fractions were lyophilized to afford the title compound as a solid. Purity was determined by LCMS (ES MS, M++H found:432) and proton NMR (400 MHz, CDCl3: δ 7.86 (1H,s), 7.45(1H,dt, J=5.7 and 8.1 Hz), 7.35 (1H, t, J=7.8 Hz), 7.20–7.00 (4H,m), 6.59 (1H, m), 5.61(1H, s), 4.54 (2H, d,J=6.0 Hz), 3.74(3H,s), 1.68(2H,m), 1.12 (2H,m) ppm.

Fuente