2H-吡喃-4-胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-5-Fluoro-N-((3-fluoro-4-methoxyphenyl)(2-methyl-2H-1,2,3-triazol-4-yl)methyl)-2-(tetrahydro-2H-pyran-4-ylamino)quinazoline-7-carboxamide (I-51) was prepared analogously except 32b was replaced with 34c, and 5-fluoro-N-((S)-(3-fluoro-4-methoxyphenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-2-((3S,4S)-3-fluorotetrahydro-2H-pyran-4-ylamino)quinazoline-7-carboxamide (I-52) was prepared analogously except 84b was replaced with 5-fluoro-2-((3S,4S)-3-fluorotetrahydro-2H-pyran-4-ylamino)quinazoline-7-carboxamide which can be prepared in accord with the procedure in example 3 except in step 3, 2H-pyran-4-amine was replaced with 60c.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,4,6-trichloro-5-nitro pyrimidine (Intermediate 37, 1 g, 4.4 mmol) in EtOH at −50° C. were added 5-methyl-1H-pyrazol-3-amine (255 mg) and DIPEA (1.6 ml) drop-wise. The resulting mixture was stirred at this temperature for 5 minutes whereupon 4-amino pyran (300 mg) was added. The resulting mixture was allowed to warm to ambient temperature for 4 hours. The mixture was diluted with H2O and EtOAc and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, saturated NaHCO3 (aq) solution, dried and evaporation of the volatiles under reduced pressure gave a colored residue. Purification by Gilson (MeCN/H2O, 5%→95%, 15 minutes) gave the title compound (120 mg). LCMS: 354 [M+1]. was added the aqueous layer was extracted with EtOAc The combined organic layers were washed with brine, saturated NaHCO3 (aq) solution dried evaporation of the volatiles under reduced pressure gave a colored residue Purification by Gilson (MeCN/H2O, 5%→95%, 15 minutes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 1.1441 g (4.5 mmole) of 4-amino-benzoic acid benzotriazol-1-yl ester and 8 mL of dry dimethylformamide was added 0.6575 g (6.5 mmole) of 4-amino-pyran followed by 0.4554 g (0.45 mmole) of triethylamine. The mixture stirred at room temperature for 90 minutes. Volatiles were removed under reduced pressure and the residue taken up in ethyl acetate, and the organic layer washed once with 100 mL of 0.5 M sodium carbonate, twice with 75 mL water, and then 75 mL brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 0.5378 g 4-amino-N-(tetrahydro-pyran-4-yl)-benzamide, which was used without further purification. Volatiles were removed under reduced pressure the organic layer washed once with 100 mL of 0.5 M sodium carbonate, twice with 75 mL water 75 mL brine, dried over anhydrous sodium sulfate concentrated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-5-Fluoro-N-((3-fluoro-4-methoxyphenyl)(2-methyl-2H-1,2,3-triazol-4-yl)methyl)-2-(tetrahydro-2H-pyran-4-ylamino)quinazoline-7-carboxamide (I-51) was prepared analogously except 32b was replaced with 34c, and 5-fluoro-N-((S)-(3-fluoro-4-methoxyphenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-2-((3S,4S)-3-fluorotetrahydro-2H-pyran-4-ylamino)quinazoline-7-carboxamide (I-52) was prepared analogously except 84b was replaced with 5-fluoro-2-((3S,4S)-3-fluorotetrahydro-2H-pyran-4-ylamino)quinazoline-7-carboxamide which can be prepared in accord with the procedure in example 3 except in step 3, 2H-pyran-4-amine was replaced with 60c.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,4,6-trichloro-5-nitro pyrimidine (Intermediate 37, 1 g, 4.4 mmol) in EtOH at −50° C. were added 5-methyl-1H-pyrazol-3-amine (255 mg) and DIPEA (1.6 ml) drop-wise. The resulting mixture was stirred at this temperature for 5 minutes whereupon 4-amino pyran (300 mg) was added. The resulting mixture was allowed to warm to ambient temperature for 4 hours. The mixture was diluted with H2O and EtOAc and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, saturated NaHCO3 (aq) solution, dried and evaporation of the volatiles under reduced pressure gave a colored residue. Purification by Gilson (MeCN/H2O, 5%→95%, 15 minutes) gave the title compound (120 mg). LCMS: 354 [M+1]. was added the aqueous layer was extracted with EtOAc The combined organic layers were washed with brine, saturated NaHCO3 (aq) solution dried evaporation of the volatiles under reduced pressure gave a colored residue Purification by Gilson (MeCN/H2O, 5%→95%, 15 minutes)