(2,5-difluorophenyl)methanamine

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: Following the procedure as describe in Example 9, making variations as required to replace 4-fluorobenzylamine with 2,5-difluorobenzylamine to react with 2-(3-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid, the title compound was obtained as a white powder in 76% yield: mp 176-177° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.37-6.87 (m, 8H), 6.06 (t, J=5.7 Hz, 1H), 4.56 (d, J=5.7 Hz, 2H), 4.46 (s, 2H), 4.05 (t, J=8.1 Hz, 2H), 3.44 (t, J=8.1 Hz, 2H), 2.58 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 162.5, 158.4, 157.4, 155.3, 155.2, 153.5, 135.5, 128.9, 128.3, 128.0, 127.0, 126.8, 116.8, 115.4, 48.0, 42.0, 41.6, 37.6, 17.2; MS (ES+) m/z 443.2 (M+1).

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

実験手順: prepared by reaction of 1-(3,4-Dimethoxy-benzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and 2-bromoacetyl bromide with 2,5-difluorobenzylamine

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

実験手順: prepared by reaction of 1-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and 2-bromoacetyl bromide with 2,5-difluorobenzylamine

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: prepared by reaction of 1-(3,4-Dimethoxy-benzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and 2-bromoacetyl bromide with 2,5-difluorobenzylamine

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

実験手順: prepared by reaction of 1-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and 2-bromoacetyl bromide with 2,5-difluorobenzylamine

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

実験手順: Following the procedure as describe in Example 9, making variations as required to replace 4-fluorobenzylamine with 2,5-difluorobenzylamine to react with 2-(3-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid, the title compound was obtained as a white powder in 76% yield: mp 176-177° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.37-6.87 (m, 8H), 6.06 (t, J=5.7 Hz, 1H), 4.56 (d, J=5.7 Hz, 2H), 4.46 (s, 2H), 4.05 (t, J=8.1 Hz, 2H), 3.44 (t, J=8.1 Hz, 2H), 2.58 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 162.5, 158.4, 157.4, 155.3, 155.2, 153.5, 135.5, 128.9, 128.3, 128.0, 127.0, 126.8, 116.8, 115.4, 48.0, 42.0, 41.6, 37.6, 17.2; MS (ES+) m/z 443.2 (M+1).

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

実験手順: In a manner analogous to the method described in example 163, {1-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-acetic acid was reacted with 2,5-difluorobenzylamine (Aldrich) to give the title product. LC-MS (ES+) 790 [(M+H)+].

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

実験手順: A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (48 mg, 0.185 mmol), 2,5-difluorobenzylamine (0.026 mL, 0.222 mmol), Pd2(dba)3 (6 mg, 0.0066 mmol), rac-BINAP (21 mg, 0.021 mmol) and NaOtBu (45 mg, 0.468 mmol) in DMA (3 mL) was heated in a microwave at 90° C. for 5 minutes. The mixture was allowed to cool, diluted with EtOAc and washed with water. The organic layer was washed with sat.aq. NaHCO3, brine and dried (Na2SO4). Column chromatography (Hex/EtOAc) afforded 4-chloro-6-(2,5-difluoro-benzylamino)-2H-phthalazin-1-one (3 mg) as an off white solid, 1H (400 MHz, CDCl3) δ: 4.46 (s, 2H), 6.90 (m, 2H), 7.00 (m, 3H), 8.10 (d, 1H), 10.09 (s, 1H) ppm; m/z (M+1) 321.98. to cool washed with water The organic layer was washed with sat.aq NaHCO3, brine and dried (Na2SO4)

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

実験手順: 7-bromo-1-(2,5-difluorobenzyl)-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine was prepared as described in Example 1, from 2-amino-3,5-dibromopyrazine as described in Example 1 by replacing 2-chloro-3,6-difluorobenzylamine in step 1 with 2,5-difluorobenzylamine.

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

実験手順: A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (48 mg, 0.185 mmol), 2,5-difluorobenzylamine (0.026 mL, 0.222 mmol), Pd2(dba)3 (6 mg, 0.0066 mmol), rac-BINAP (21 mg, 0.021 mmol) and NaOtBu (45 mg, 0.468 mmol) in DMA (3 mL) was heated in a microwave at 90° C. for 5 minutes. The mixture was allowed to cool, diluted with EtOAc and washed with water. The organic layer was washed with sat.aq. NaHCO3, brine and dried (Na2SO4). Column chromatography (Hex/EtOAc) afforded 4-chloro-6-(2,5-difluoro-benzylamino)-2H-phthalazin-1-one (3 mg) as an off white solid, 1H (400 MHz, CDCl3) δ: 4.46 (s, 2H), 6.90 (m, 2H), 7.00 (m, 3H), 8.10 (d, 1H), 10.09 (s, 1H) ppm; m/z (M+1) 321.98. to cool washed with water The organic layer was washed with sat.aq NaHCO3, brine and dried (Na2SO4)