(4-methylphenyl)methanesulfonyl chloride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In dimethylformamide (90 ml) is dispersed sodium p-methylbenzylsulfonate (30 g, 0.145 mol) which is sufficientry dry. The dispersion is cooled to -10° C. and under stirring, thionyl chloride (19.2 ml, 0.29 mol) is added dropwise. The mixture is stirred at room temperature for 3 hours and poured in ice-water (500 g) and extracted with ether (3 times, 150 ml each). The ethereal layers are combined, washed twice with cold water and dried over sodium sulfate. The ether is distilled off and petroleum ether is added to the crystalline residue, followed by cooling. The crystals are collected by filtration. The mixture is stirred at room temperature for 3 hours extracted with ether (3 times, 150 ml each) washed twice with cold water dried over sodium sulfate The ether is distilled off petroleum ether is added to the crystalline residue by cooling The crystals are collected by filtration

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

Procedure: A solution of (3-amino-propyl)-{2-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-dimethyl-ammonium bromide (Intermediate M) (0.30 g, 0.756 mmol), p-tolyl-methanesulfonyl chloride (0.16 g, 0.76 mmol) and N-methylmorpholine (0.4 mL, 3.64 mmol) in DMF (5 mL) is shaken at RT for 16 h. The solvent is removed in vacuo and the residue is subjected to chromatography (basic alumina; 0-15% methanol in DCM) to yield the title compound. M+ 484. The solvent is removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Potassium tert-butoxide (93.8 mg, 836 μmol) was added to a solution of 2-amino-5-(benzyloxy)-N,1-dimethyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide (110 mg, 380 μmol) in THF (10 ml) in DMF (2 ml) [Comment: please check]. After 10 min., the reaction mixture was cooled by an ice bath and then a solution of (4-methylphenyl)methanesulfonyl chloride (93.7 mg, 458 μmol) in THF (2 ml) was added. After 70 min., EtOAc and 1 N NaOH aqueous solution were added. The organic phase was extracted with EtOAc and then with DCM. The combined organic phases were washed with water, and brine, dried over Na2SO4 and evaporated to dryness. Chromatography (silica gel, 0 to 2% MeOH in DCM) provided the title compound as a pale yellow solid (0.080 g; 46%). LCMS: m/z=457 (MH+). the reaction mixture was cooled by an ice bath After 70 min. The organic phase was extracted with EtOAc The combined organic phases were washed with water, and brine dried over Na2SO4 evaporated to dryness

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In dimethylformamide (90 ml) is dispersed sodium p-methylbenzylsulfonate (30 g, 0.145 mol) which is sufficientry dry. The dispersion is cooled to -10° C. and under stirring, thionyl chloride (19.2 ml, 0.29 mol) is added dropwise. The mixture is stirred at room temperature for 3 hours and poured in ice-water (500 g) and extracted with ether (3 times, 150 ml each). The ethereal layers are combined, washed twice with cold water and dried over sodium sulfate. The ether is distilled off and petroleum ether is added to the crystalline residue, followed by cooling. The crystals are collected by filtration. The mixture is stirred at room temperature for 3 hours extracted with ether (3 times, 150 ml each) washed twice with cold water dried over sodium sulfate The ether is distilled off petroleum ether is added to the crystalline residue by cooling The crystals are collected by filtration

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

Procedure: A solution of (3-amino-propyl)-{2-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-dimethyl-ammonium bromide (Intermediate M) (0.30 g, 0.756 mmol), p-tolyl-methanesulfonyl chloride (0.16 g, 0.76 mmol) and N-methylmorpholine (0.4 mL, 3.64 mmol) in DMF (5 mL) is shaken at RT for 16 h. The solvent is removed in vacuo and the residue is subjected to chromatography (basic alumina; 0-15% methanol in DCM) to yield the title compound. M+ 484. The solvent is removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir: