methyl 2-(2-aminophenyl)acetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 2-aminophenylacetate (3.0 g, 18.2 mmol) and 1-tert-butoxycarbonyl-4-piperidone (4.5 g, 22.6 mmol) were set stirring in 50 mL of CH2Cl2 under an atmosphere of nitrogen. Sodium triacetoxyborohydride (5.4 g, 25.5 mmol) was added followed by 1 mL of acetic acid. After 20 h at rt the mixture was quenched by the slow addition of saturated NaHCO3. After stirring for 30 min, the organics were separated, dried (MgSO4), and evaporated to afford 7.5 g of a purple oil. Purification by column chromatography (silica, 10-50% EtOAc/hexanes) gave 3.9 g (62%) of the title compound. TLC (silica, 25% EtOAc/hexanes): Rf=0.15. 1H NMR (400 MHz, CDCl3): 7.25 (m, 2H), 7.01 (m, 2H), 4.40 (m, 1H), 3.53 (s, 2H), 2.83 (m, 2H), 2.32 (m, 2H), 1.70 (m, 2H), 1.51 (s, 9H). After 20 h at rt the mixture was quenched by the slow addition of saturated NaHCO3 the organics were separated dried (MgSO4) evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 2-aminophenylacetate (3.0 g, 18.2 mmol) and 1-tert-butoxycarbonyl-4-piperidone (4.5 g, 22.6 mmol) were set stirring in 50 mL of CH2Cl2 under an atmosphere of nitrogen. Sodium triacetoxyborohydride (5.4 g, 25.5 mmol) was added followed by 1 mL of acetic acid. After 20 h at rt the mixture was quenched by the slow addition of saturated NaHCO3. After stirring for 30 min, the organics were separated, dried (MgSO4), and evaporated to afford 7.5 g of a purple oil. Purification by column chromatography (silica, 10-50% EtOAc/hexanes) gave 3.9 g (62%) of the title compound. TLC (silica, 25% EtOAc/hexanes): Rf=0.15. 1H NMR (400 MHz, CDCl3): 7.25 (m, 2H), 7.01 (m, 2H), 4.40 (m, 1H), 3.53 (s, 2H), 2.83 (m, 2H), 2.32 (m, 2H), 1.70 (m, 2H), 1.51 (s, 9H). After 20 h at rt the mixture was quenched by the slow addition of saturated NaHCO3 the organics were separated dried (MgSO4) evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 2-nitrophenylacetate (10.1 g, 51.2 mmol) in 125 mL of methanol containing 221 mg of 10% Pd/C was placed on the Parr hydrogenator at 40 psi. After 5 h the mixture was filtered through celite and evaporated under reduced pressure to give a clear red oil. The solvent was evaporated under reduced pressure to give 8.5 g (100%) of methyl 2-aminophenylacetate as a clear red oil. TLC (silica, EtOAc/hexanes): Rf=0.24. 1H NMR (400 MHz, CDCl3): 7.21 (m, 2H), 6.86 (m, 2H), 3.81 (s, 3H), 3.70 (s, 2H). After 5 h the mixture was filtered through celite evaporated under reduced pressure to give a clear red oil The solvent was evaporated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A procedure similar to that described in Example 52 was carried out with 9-bromo-5-carboxymethyl-6,7-dihydro-1H, 5 H-pyrido[1,2,3-de]quinoxaline-2,3-dione (340 mg, 1 mmol) and o-methoxycarbonylmethylaniline (180 mg, 1 mmol) to give 340 mg of the title compound (70%): mp 206°~207° C. (dec); 1H NMR (270 MHz, DMSO-d6) δ12.06 (bs, 1H), 9.51 (s, 1H), 7.36 (bd, 1H, J=8.6 Hz), 7.26~7.29 (m, 3H), 7.16~7.19 (m, 2H), 5.16~5.25 (m, 1H), 3.70 (s, 2H), 3.59 (s, 3H), 3.07 (ddd, 1H, J=17.1, 13.5, 4.5 Hz), 2.83 (dm, 1H, J=17.1 Hz), 2.60 (d, 2H, J=7.6 Hz), 2.11 (dm, 1H, J=13.5 Hz), 1.80~1.96 (m, 1H).

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A procedure similar to that described in Example 52 was carried out with 9-bromo-5-carboxymethyl-6,7-dihydro-1H, 5 H-pyrido[1,2,3-de]quinoxaline-2,3-dione (340 mg, 1 mmol) and o-methoxycarbonylmethylaniline (180 mg, 1 mmol) to give 340 mg of the title compound (70%): mp 206°~207° C. (dec); 1H NMR (270 MHz, DMSO-d6) δ12.06 (bs, 1H), 9.51 (s, 1H), 7.36 (bd, 1H, J=8.6 Hz), 7.26~7.29 (m, 3H), 7.16~7.19 (m, 2H), 5.16~5.25 (m, 1H), 3.70 (s, 2H), 3.59 (s, 3H), 3.07 (ddd, 1H, J=17.1, 13.5, 4.5 Hz), 2.83 (dm, 1H, J=17.1 Hz), 2.60 (d, 2H, J=7.6 Hz), 2.11 (dm, 1H, J=13.5 Hz), 1.80~1.96 (m, 1H).

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Stir the mixture of methyl 2-(2-aminophenyl)acetate (4.8 g, 29.1 mmol) and potassium carbonate (8.0 g, 58.2 mmol) in DMF (15 mL) at room temperature overnight. TLC (PE:EtOAc=2:1) shows the reaction is complete. Concentrate the reaction mixture under reduced pressure to give the crude product. Purify by chromatography (silica gel, EtOAc:PE=1:2) to afford the title compound (4.0 g, 95%). MS: (M+1): 134.2. Concentrate the reaction mixture under reduced pressure to give the crude product Purify by chromatography (silica gel, EtOAc:PE=1:2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add Pd/C (10%, 800 mg) to a solution of methyl 2-(2-nitrophenyl)acetate (7.5 g, 38.5 mmol) in methanol (50 mL) under N2, then flush with H2, stir the reaction under H2 atmosphere at room temperature overnight. Remove the hydrogen; filter off the solid, concentrate the filtrate under reduced pressure to obtain the crude product (4.8 g, 76.2%) which is used directly without further purification. MS: (M+1):166. flush with H2 the reaction under H2 atmosphere at room temperature overnight Remove the hydrogen filter off the solid concentrate the filtrate under reduced pressure