oxane-4-sulfonyl chloride

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

実験手順: Prepared according to procedures described above, by reacting tetrahydro-2H-pyran-4-sulfonyl chloride with N—((S)-1-(((S)-1-(((2S,4R)-4,5-dihydroxy-4-methyl-3-oxo-1-phenylpentan-2-yl)amino)-3-methoxy-1-oxopropan-2-yl)amino)-3-methoxy-1-oxopropan-2-yl)-2-methylthiazole-5-carboxamide. MS for C30H42N4O11S2 m/z: 699 (M+H)+. Prepared

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

実験手順: Tetrahydropyran-4-sulfonyl chloride (16.28 mg, 0.08815 mmol) was added to a suspension of 2-amino-6-fluoro-N-(5-fluoro-4-piperazin-1-yl-3-pyridyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (30 mg, 0.08014 mmol) (synthesized according to the procedure similar to Example 2) and Et3N (12.16 mg, 16.75 μL, 0.1202 mmol) in DMF (0.2 mL). The crude mixture was purified by Fractionlynx HPLC. The clean aqueous fractions were combined and lyophilised, yielding 2-amino-6-fluoro-N-(5-fluoro-4-(4-((tetrahydro-2H-pyran-4-yl)sulfonyl)piperazin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. MS (ES+) 523.1. synthesized The crude mixture was purified by Fractionlynx HPLC

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

実験手順: Tetrahydropyran-4-sulfonyl chloride (16.28 mg, 0.08815 mmol) was added to a suspension of 2-amino-6-fluoro-N-(5-fluoro-4-piperazin-1-yl-3-pyridyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (30 mg, 0.08014 mmol) (synthesized according to the procedure similar to Example 2) and Et3N (12.16 mg, 16.75 μL, 0.1202 mmol) in DMF (0.2 mL). The crude mixture was purified by Fractionlynx HPLC. The clean aqueous fractions were combined and lyophilised, yielding 2-amino-6-fluoro-N-(5-fluoro-4-(4-((tetrahydro-2H-pyran-4-yl)sulfonyl)piperazin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. MS (ES+) 523.1. synthesized The crude mixture was purified by Fractionlynx HPLC

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

実験手順: Prepared according to procedures described above, by reacting tetrahydro-2H-pyran-4-sulfonyl chloride with N—((S)-1-(((S)-1-(((2S,4R)-4,5-dihydroxy-4-methyl-3-oxo-1-phenylpentan-2-yl)amino)-3-methoxy-1-oxopropan-2-yl)amino)-3-methoxy-1-oxopropan-2-yl)-2-methylthiazole-5-carboxamide. MS for C30H42N4O11S2 m/z: 699 (M+H)+. Prepared

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-(3-Ethoxy-5-hydroxy-4-iodo-benzyl)-pyrimidine-2,4-diamine (see example 32 stage a) (2,300 mg; 5.96 mmol) is dissolved in tetrahydrofuran (70 ml), potassium tert-butylate (1,000 mg; 8.9 mmol) is added and the mixture is cooled to −20° C. Tetrahydropyran-4-sulphonyl chloride (2.2 g; 11.9 mmol) is added at this temperature and the mixture is then stirred for one hour at −20° C. The reaction mixture is poured on to ice-water and extracted twice with ethyl acetate. The organic phase is dried over sodium sulphate, the salts are filtered off and the solvent is evaporated off. The residue is chromatographed over silica gel with methylene chloride 1 methanol (19/1) and 0.5% ammonia. The pure fractions are co mbidand the solvent is evaporated off. extracted twice with ethyl acetate The organic phase is dried over sodium sulphate the salts are filtered off the solvent is evaporated off The residue is chromatographed over silica gel with methylene chloride 1 methanol (19/1) and 0.5% ammonia is evaporated off

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

実験手順: Following the procedure as described in Example 38 step 4 and making variations as required to replace 4-(adamantan-1-ylmethoxy)-3-(2-methoxypyridin-3-yl)benzamide with 4-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzamide and to replace methanesulfonyl chloride with tetrahydro-2H-pyran-4-sulfonyl chloride, the title compound was obtained as a colorless solid (0.15 g, 30%): 1H NMR (300 MHz, CDCl3) δ8.55-8.44 (m, 1H), 7.60-7.52 (m, 1H), 6.62-6.52 (m, 1H), 4.17-3.90 (m, 3H), 3.56 (s, 2H), 3.47-3.36 (m, 2H), 2.12-1.95 (m, 8H), 1.84-1.65 (m, 12H), 1.00-0.90 (m, 2H), 0.71-0.58 (m, 2H); MS (ES+) m/z 492.21 (M+1).

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

実験手順: Tetrahydropyran-4-sulfonyl chloride (16.28 mg, 0.08815 mmol) was added to a suspension of 2-amino-6-fluoro-N-(5-fluoro-4-piperazin-1-yl-3-pyridyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (30 mg, 0.08014 mmol) (synthesized according to the procedure similar to Example 2) and Et3N (12.16 mg, 16.75 μL, 0.1202 mmol) in DMF (0.2 mL). The crude mixture was purified by Fractionlynx HPLC. The clean aqueous fractions were combined and lyophilised, yielding 2-amino-6-fluoro-N-(5-fluoro-4-(4-((tetrahydro-2H-pyran-4-yl)sulfonyl)piperazin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. MS (ES+) 523.1. synthesized The crude mixture was purified by Fractionlynx HPLC