2-methylmorpholine

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

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

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

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

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

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

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

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: To a mixture of 112 mg (0.244 mmol) of 5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid, 70 mg (0.70 mmol) of 2-methylmorpholine and 0.174 mL (1.0 mmol) of DIEA in CH2Cl2 (2.5 mL) was added 0.19 mL 1-propanephosphonic acid cyclic anhydride (50% in ethyl acetate). After 3 h the reaction mixture was directly purified via flash column (50% EtOAc in hexane) to afford 67 mg of 4-chloro-N-[5-chloro-2-(3-methyl-morpholine-4-carbonyl)-pyridin-3-yl]-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide as a white powder. MS m/z: 542.36 (M+H). After 3 h the reaction mixture was directly purified via flash column (50% EtOAc in hexane)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Chloromethyl)-N-[6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (50 mg, 0.091 mmol) and 2-methylmorpholine (0.5 mL, 0.091 mmol) were put in a 0.5-2 mL vial then heated in the microwave at 90° C. for 15 min. The solvent was blown down under nitrogen. Isopropanol (2 mL) and 2M NaOH (2.000 mL) were added and the reaction mixture was stirred for 3 hr at 25° C., then neutralised with 2M HCl aqueous solution until pH=7 (checking with pH paper). The solvent was removed under nitrogen. The mixture was dissolved in 2 mL of DMSO and passed through a hydrophobic frit. Purification was carried out by MDAP to afford the title compound (10 mg). The solvent was removed under nitrogen The mixture was dissolved in 2 mL of DMSO Purification

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Chloromethyl)-N-[6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (50 mg, 0.091 mmol) and 2-methylmorpholine (0.5 mL, 0.091 mmol) were put in a 0.5-2 mL vial then heated in the microwave at 90° C. for 15 min. The solvent was blown down under nitrogen. Isopropanol (2 mL) and 2M NaOH (2.000 mL) were added and the reaction mixture was stirred for 3 hr at 25° C., then neutralised with 2M HCl aqueous solution until pH=7 (checking with pH paper). The solvent was removed under nitrogen. The mixture was dissolved in 2 mL of DMSO and passed through a hydrophobic frit. Purification was carried out by MDAP to afford the title compound (10 mg). The solvent was removed under nitrogen The mixture was dissolved in 2 mL of DMSO Purification