3-(2-hydroxyethyl)benzonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound or its salt was prepared by a procedure similar to that described for E11 starting from of 3-(2-hydroxyethyl)benzonitrile and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound or its salt was prepared by a procedure similar to that described for E11 starting from of 3-(2-hydroxyethyl)benzonitrile and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was obtained following procedure and work up described for Intermediate 47 step 2 but starting from 3-(2-hydroxy-ethyl)-benzonitrile (2 g, 13.59 mmol). Lyophilization of the reaction mixture gave the title compound as a white powder. 1H NMR (DMSO-d6, 300 MHz) δ 9.56 (s, 1H), 7.51-7.46 (m, 2H), 7.28-7.19 (m, 2H), 5.75 (bs, 2H), 4.64 (t, J=5.2 Hz, 1H), 3.63-3.57 (m, 2H), 2.71 (t, J=7.1 Hz, 2H). LC/MS (Method B): 181.1 (M+H)+.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-(2-hydroxy-ethyl)-benzonitrile (1 g; 6.79 mmol) in toluene (20 mL), was added tetrabutylammonium hydrogen sulfate (230.70 mg; 0.68 mmol; 0.10 eq.) and NaOH (20 mL; 5 M; 10 mmol) followed by the addition of tert-butyl bromoacetate (2 mL; 13.59 mmol). Reaction mixture was stirred at RT under vigorous stirring for 9 h. After this time, the aqueous phase was removed and the organic phase was diluted with EtOAc (50 mL), washed with water (50 mL) and brine (50 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give the title compound as a yellow powder (1.42 g; 80%). 1H NMR (DMSO-d6, 300 MHz) δ 7.74-7.73 (m, 1H), 7.68-7.65 (m, 1H), 7.63-7.59 (m, 1H), 7.51-7.46 (m, 1H), 3.97 (s, 2H), 3.69 (t, J=6.5 Hz, 2H), 2.88 (t, J=6.5 Hz, 2H), 1.40 (s, 9H). LC/MS (Method B): 262.1 (M+H)+. Reaction mixture under vigorous stirring for 9 h After this time, the aqueous phase was removed the organic phase was diluted with EtOAc (50 mL) washed with water (50 mL) and brine (50 mL) The combined organic layers were dried over magnesium sulfate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was obtained following procedure and work up described for Intermediate 47 step 2 but starting from 3-(2-hydroxy-ethyl)-benzonitrile (2 g, 13.59 mmol). Lyophilization of the reaction mixture gave the title compound as a white powder. 1H NMR (DMSO-d6, 300 MHz) δ 9.56 (s, 1H), 7.51-7.46 (m, 2H), 7.28-7.19 (m, 2H), 5.75 (bs, 2H), 4.64 (t, J=5.2 Hz, 1H), 3.63-3.57 (m, 2H), 2.71 (t, J=7.1 Hz, 2H). LC/MS (Method B): 181.1 (M+H)+.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-(2-hydroxy-ethyl)-benzonitrile (1 g; 6.79 mmol) in toluene (20 mL), was added tetrabutylammonium hydrogen sulfate (230.70 mg; 0.68 mmol; 0.10 eq.) and NaOH (20 mL; 5 M; 10 mmol) followed by the addition of tert-butyl bromoacetate (2 mL; 13.59 mmol). Reaction mixture was stirred at RT under vigorous stirring for 9 h. After this time, the aqueous phase was removed and the organic phase was diluted with EtOAc (50 mL), washed with water (50 mL) and brine (50 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give the title compound as a yellow powder (1.42 g; 80%). 1H NMR (DMSO-d6, 300 MHz) δ 7.74-7.73 (m, 1H), 7.68-7.65 (m, 1H), 7.63-7.59 (m, 1H), 7.51-7.46 (m, 1H), 3.97 (s, 2H), 3.69 (t, J=6.5 Hz, 2H), 2.88 (t, J=6.5 Hz, 2H), 1.40 (s, 9H). LC/MS (Method B): 262.1 (M+H)+. Reaction mixture under vigorous stirring for 9 h After this time, the aqueous phase was removed the organic phase was diluted with EtOAc (50 mL) washed with water (50 mL) and brine (50 mL) The combined organic layers were dried over magnesium sulfate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound or its salt was prepared by a procedure similar to that described for E11 starting from of 3-(2-hydroxyethyl)benzonitrile and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was obtained following procedure and work up described for Intermediate 47 step 2 but starting from 3-(2-hydroxy-ethyl)-benzonitrile (2 g, 13.59 mmol). Lyophilization of the reaction mixture gave the title compound as a white powder. 1H NMR (DMSO-d6, 300 MHz) δ 9.56 (s, 1H), 7.51-7.46 (m, 2H), 7.28-7.19 (m, 2H), 5.75 (bs, 2H), 4.64 (t, J=5.2 Hz, 1H), 3.63-3.57 (m, 2H), 2.71 (t, J=7.1 Hz, 2H). LC/MS (Method B): 181.1 (M+H)+.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-(2-hydroxy-ethyl)-benzonitrile (1 g; 6.79 mmol) in toluene (20 mL), was added tetrabutylammonium hydrogen sulfate (230.70 mg; 0.68 mmol; 0.10 eq.) and NaOH (20 mL; 5 M; 10 mmol) followed by the addition of tert-butyl bromoacetate (2 mL; 13.59 mmol). Reaction mixture was stirred at RT under vigorous stirring for 9 h. After this time, the aqueous phase was removed and the organic phase was diluted with EtOAc (50 mL), washed with water (50 mL) and brine (50 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give the title compound as a yellow powder (1.42 g; 80%). 1H NMR (DMSO-d6, 300 MHz) δ 7.74-7.73 (m, 1H), 7.68-7.65 (m, 1H), 7.63-7.59 (m, 1H), 7.51-7.46 (m, 1H), 3.97 (s, 2H), 3.69 (t, J=6.5 Hz, 2H), 2.88 (t, J=6.5 Hz, 2H), 1.40 (s, 9H). LC/MS (Method B): 262.1 (M+H)+. Reaction mixture under vigorous stirring for 9 h After this time, the aqueous phase was removed the organic phase was diluted with EtOAc (50 mL) washed with water (50 mL) and brine (50 mL) The combined organic layers were dried over magnesium sulfate filtered concentrated