oxan-4-ylmethanesulfonyl chloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-(1-((5-(2-Aminopyridin-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (80 mg, 0.13 mmol) was treated with (tetrahydro-2H-pyran-4-yl)methanesulfonyl chloride (26 mg, 0.13 mmol) and triethylamine (36 μl, 0.26 mmol) in pyridine (2 ml) according to the method described in Preparation 15b. The residue was purified using SP1® Purification System (hexane-ethyl acetate) to give 55 mg (53% yield) of the title compound. Purity 98%. The residue was purified SP1® Purification System (hexane-ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-(1-((5-(2-Aminopyridin-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (80 mg, 0.13 mmol) was treated with (tetrahydro-2H-pyran-4-yl)methanesulfonyl chloride (26 mg, 0.13 mmol) and triethylamine (36 μl, 0.26 mmol) in pyridine (2 ml) according to the method described in Preparation 15b. The residue was purified using SP1® Purification System (hexane-ethyl acetate) to give 55 mg (53% yield) of the title compound. Purity 98%. The residue was purified SP1® Purification System (hexane-ethyl acetate)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-(1-((5-(4-Amino-2-methoxyphenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (50 mg, 0.08 mmol) was treated with pyridine (19 μL, 0.23 mmol) and (tetrahydro-2H-pyran-4-yl)methanesulfonyl chloride (31 mg, 0.16 mmol) in tetrahydrofuran (0.5 ml) according to the method described in Preparation 175 but stirring at 50° C. overnight. The title compound was obtained (54 mg, 68% yield, 80% purity) without further purification. described in Preparation 175

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-(1-((5-(4-Amino-2-methoxyphenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (50 mg, 0.08 mmol) was treated with pyridine (19 μL, 0.23 mmol) and (tetrahydro-2H-pyran-4-yl)methanesulfonyl chloride (31 mg, 0.16 mmol) in tetrahydrofuran (0.5 ml) according to the method described in Preparation 175 but stirring at 50° C. overnight. The title compound was obtained (54 mg, 68% yield, 80% purity) without further purification. described in Preparation 175

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared by a similar method to example 3 using (2R,3R,4S,5R)-2-{2-(aminomethyl)-6-[(2,2-diphenylethyl)amino}-9H-purin-9-yl}-5-(methoxymethyl)tetrahydro-3,4-furandiol (example 1) (245 mg, 0.48 mmol), tetrahydro-2H-pyran-4-ylmethanesulfonyl chloride (preparation 21) (95 mg, 0.48 mmol), triethylamine (145 mg, 1.44 mmol) in tetrahydrofuran (23 ml). Purification by column chromatography on silica gel eluting with a solvent system of dichloromethane:methanol:ammonia (95:5:0.25) gave the title compound as an oil (118 mg). MS: 654 (MH+). Purification by column chromatography on silica gel eluting with a solvent system of dichloromethane:methanol:ammonia (95:5:0.25)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: MS (ESI): 331 (MNa+); 4-(chlorosulfonylmethyl)tetrahydropyran-4-(carboxylic acid benzyl ester): MS (ESI): 354 (MNa+); 4-[4-(4-fluorophenyl)piperazine-1-sulfonylmethyl]tetrahydropyran-4-carboxylic acid benzyl ester: MS (ESI): 477 (MH+), 499 (MNa+); 4-[4-(4-fluorophenyl)piperazine-1-sulfonylmethyl]tetrahydropyran-4-carboxylic acid: MS (ESI): 387 (MH+), 409 (MNa+).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-(1-((5-(2-Aminopyridin-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (80 mg, 0.13 mmol) was treated with (tetrahydro-2H-pyran-4-yl)methanesulfonyl chloride (26 mg, 0.13 mmol) and triethylamine (36 μl, 0.26 mmol) in pyridine (2 ml) according to the method described in Preparation 15b. The residue was purified using SP1® Purification System (hexane-ethyl acetate) to give 55 mg (53% yield) of the title compound. Purity 98%. The residue was purified SP1® Purification System (hexane-ethyl acetate)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-(1-((5-(4-Amino-2-methoxyphenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (50 mg, 0.08 mmol) was treated with pyridine (19 μL, 0.23 mmol) and (tetrahydro-2H-pyran-4-yl)methanesulfonyl chloride (31 mg, 0.16 mmol) in tetrahydrofuran (0.5 ml) according to the method described in Preparation 175 but stirring at 50° C. overnight. The title compound was obtained (54 mg, 68% yield, 80% purity) without further purification. described in Preparation 175