2-methyl-2-piperazin-1-ylpropanamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: 4-(6-(Bromomethyl)-2-chloropyrido[3,2-d]pyrimidin-4-yl)morpholine 7 (0.1 g) was reacted with 2-methyl-2-(piperazin-1-yl)propanamide via General Procedure B to give 123 mg of 2-(4-((2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide.

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

実験手順: 4-(6-(Bromomethyl)-2-chloropyrido[3,2-d]pyrimidin-4-yl)morpholine 7 (0.1 g) was reacted with 2-methyl-2-(piperazin-1-yl)propanamide via General Procedure B to give 123 mg of 2-(4-((2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide.

反応条件: temp:0.00; pressure:0.00; stir:

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: 4-(6-(Bromomethyl)-2-chloropyrido[3,2-d]pyrimidin-4-yl)morpholine 7 (0.1 g) was reacted with 2-methyl-2-(piperazin-1-yl)propanamide via General Procedure B to give 123 mg of 2-(4-((2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide.

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

実験手順: To a solution of (2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)acetaldehyde (110 mg, 0.37 mmol) in DCE (10 mL) was added 2-piperazin-1-ylisobutyramide (90 mg, 0.53 mmol), trimethyl orthoformate (0.20 mL, 1.86 mmol) and acetic acid (0.02 mL, 0.37 mmol). The reaction mixture was stirred at room temperature for 3 h, sodium triacetoxyborohydride (118 mg, 0.56 mmol) was added and the resulting mixture stirred for a further 2 days. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, the cartridge was washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by column chromatography (Si—PCC, 0-20% MeOH in EtOAc) to give the title compound as a pale yellow solid (71 mg, 42%). LCMS (Method H): RT=2.40 min, [M+H]+ 451.5 the resulting mixture stirred for a further 2 days the cartridge was washed with MeOH the desired product eluted with 2 M NH3 in MeOH The resulting residue was purified by column chromatography (Si—PCC, 0-20% MeOH in EtOAc)

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

実験手順: To a solution of 2-chloro-7-methyl-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-carbaldehyde (1.00 g, 3.36 mmol) in DCE (50 mL) was added 2-(piperazin-1-yl)isobutyramide (630 mg, 3.69 mmol), trimethyl orthoformate (3.67 mL, 33.58 mmol) and acetic acid (0.19 mL, 3.36 mmol). After stirring at room temperature for 3 h sodium triacetoxyborohydride (1.10 g, 5.03 mmol) was added and the resulting mixture stirred for a further 17 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH/DCM. The resultant residue was triturated with MeOH to give 2-[4-(2-Chloro-7-methyl-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide as a white solid (1.12 g, 74%). LCMS (Method C): RT=2.88 min, [M+H]+ 453 was added washed with MeOH then eluted with 2 M NH3 in MeOH/DCM The resultant residue was triturated with MeOH

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

実験手順: A mixture of 5-chloro-7-morpholin-4-yl-thiazolo[4,5-d]pyrimidine-2-carbaldehyde (250 mg, 0.88 mmol), 2-piperazin-1-yl-isobutyramide (173 mg, 1.01 mmol) and 4 Å molecular sieves (1.0 g) in 1,2-dichloroethane (15 mL) was stirred at RT under nitrogen atmosphere for 4 h. Sodium triacetoxyborohydride (280 mg, 1.32 mmol) was added and the resulting reaction mixture was stirred at RT for 16 h. The solvent was reduced in vacuo and the residue was loaded on an Isolute® SCX-2 cartridge (25 g). The cartridge was washed with DCM/MeOH and the desired product was subsequently eluted using a mixture of 2 M NH3 in MeOH and DCM. The resulting residue was further purified by column chromatography (Si—PCC, MeOH:DCM: gradient 0:100 to 6:94). The solvents were reduced in vacuo to afford the title compound as a yellow solid (275 mg, 60%). LCMS (Method H): RT 2.41 min, [M+H]+ 440. 1H NMR (400 MHz, CDCl3): δ 7.04 (1 H, br s), 5.22 (1 H, br s), 3.97-3.95 (6 H, m), 3.85 (4 H, t, J=4.80 Hz), 2.67 (8 H, m), 1.25 (6 H, s) the resulting reaction mixture was stirred at RT for 16 h The cartridge was washed with DCM/MeOH the desired product was subsequently eluted a mixture of 2 M NH3 in MeOH and DCM The resulting residue was further purified by column chromatography (Si—PCC, MeOH:DCM: gradient 0:100 to 6:94)

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

実験手順: To a solution of (2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)acetaldehyde (110 mg, 0.37 mmol) in DCE (10 mL) was added 2-piperazin-1-ylisobutyramide (90 mg, 0.53 mmol), trimethyl orthoformate (0.20 mL, 1.86 mmol) and acetic acid (0.02 mL, 0.37 mmol). The reaction mixture was stirred at room temperature for 3 h, sodium triacetoxyborohydride (118 mg, 0.56 mmol) was added and the resulting mixture stirred for a further 2 days. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, the cartridge was washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by column chromatography (Si—PCC, 0-20% MeOH in EtOAc) to give the title compound as a pale yellow solid (71 mg, 42%). LCMS (Method H): RT=2.40 min, [M+H]+ 451.5 the resulting mixture stirred for a further 2 days the cartridge was washed with MeOH the desired product eluted with 2 M NH3 in MeOH The resulting residue was purified by column chromatography (Si—PCC, 0-20% MeOH in EtOAc)