[methyl(sulfamoyl)amino]methane

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:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4-Dibromopyrimidine (0.50 g, 2.11 mmol), N,N-dimethylsulfamide (0.26 mg, 2.11 mmol), cesium carbonate (2.75 g, 8.44 mmol), Pd2(dba)3 (0.10 mg, 0.11 mmol), and Xantphos (0.18 mg, 0.32 mmol) were placed in a flask. Dioxane (24 mL) was added and argon was bubbled through the solution for several minutes. The reaction was then heated at 100° C. overnight. The reaction was cooled to ambient temperature, diluted with ethyl acetate, washed with saturated sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated. Reverse phase HPLC was used for purification to yield the title compound. argon was bubbled through the solution for several minutes The reaction was cooled to ambient temperature diluted with ethyl acetate washed with saturated sodium bicarbonate dried over magnesium sulfate filtered concentrated Reverse phase HPLC was used for purification

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

Procedure: 1,1′-Carbonyldiimidazole (1.17 g, 7.2 mmol) was added to a stirred solution of 2-bromo-3-cyclohexyl-1H-indole-6-carboxylic acid (2.03 g, 6.3 mmol) in THF (6 mL) at 22° C. The evolution of CO2 was instantaneous and when it slowed the solution was heated at 50° C. for 1 hr and then cooled to 22° C. N,N-Dimethylsulfamide (0.94 g, 7.56 mmol) was added followed by the dropwise addition of a solution of DBU (1.34 g, 8.8 mmol) in THF (4 mL). Stirring was continued for 24 hr. The mixture was partitioned between ethyl acetate and dilute HCl. The ethyl acetate layer washed with water followed by brine and dried over Na2SO4. The extract was concentrated to dryness to leave the title product as a pale yellow friable foam, (2.0 g, 74%, >90% purity, estimated from NMR). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.28-1.49 (m, 3H) 1.59-2.04 (m, 7H) 2.74-2.82 (m, 1H) 2.88 (s, 6H) 7.57 (dd, J=8.42, 1.46 Hz, 1H) 7.74 (d, J=8.78 Hz, 1H) 7.91 (s, 1H) 11.71 (s, 1H) 12.08 (s, 1H). cooled to 22° C The mixture was partitioned between ethyl acetate and dilute HCl The ethyl acetate layer washed with water dried over Na2SO4 The extract was concentrated to dryness

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

Procedure: 1,1′-Carbonyldiimidazole (1.17 g, 7.2 mmol) was added to a stirred solution of 2-bromo-3-cyclohexyl-1H-indole-6-carboxylic acid (2.03 g, 6.3 mmol) in THF (6 mL) at 22° C. The evolution of CO2 was instantaneous and when it slowed the solution was heated at 50° C. for 1 hr and then cooled to 22° C. N,N-Dimethylsulfamide (0.94 g, 7.56 mmol) was added followed by the dropwise addition of a solution of DBU (1.34 g, 8.8 mmol) in THF (4 mL). Stirring was continued for 24 hr. The mixture was partitioned between ethyl acetate and dilute HCl. The ethyl acetate layer washed with water followed by brine and dried over Na2SO4. The extract was concentrated to dryness to leave the title product as a pale yellow friable foam, (2.0 g, 74%, >90% purity, estimated from NMR). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.28-1.49 (m, 3H) 1.59-2.04 (m, 7H) 2.74-2.82 (m, 1H) 2.88 (s, 6H) 7.57 (dd, J=8.42, 1.46 Hz, 1H) 7.74 (d, J=8.78 Hz, 1H) 7.91 (s, 1H) 11.71 (s, 1H) 12.08 (s, 1H). cooled to 22° C The mixture was partitioned between ethyl acetate and dilute HCl The ethyl acetate layer washed with water dried over Na2SO4 The extract was concentrated to dryness

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.25 mole each of triphenyl phosphite, benzaldehyde, and N,N-dimethylsulfamide in 130g of chlorobenzene is warmed at 115° C. for 1.5 hrs. After the reaction mixture cools to room temperature, 41.0g (36% yield) of crude product is isolated by filtration. It is washed with water and recrystallized from chlorobenzene, giving a white solid: mp 193°-196°; 31P nmr (DMSO-d6) -14.0 ppm(d, J = 28Hz); 1H nmr δ8.8(d of d, 1, J = 2 and 11, NH), 6.8-7.8(m, 15, aryl), 5.2(d of d, 1, J = 10 and 25Hz, CH), 2.4(s, 6, CH3). cools to room temperature

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.25 mole each of triphenyl phosphite, benzaldehyde, and N,N-dimethylsulfamide in 130g of chlorobenzene is warmed at 115° C. for 1.5 hrs. After the reaction mixture cools to room temperature, 41.0g (36% yield) of crude product is isolated by filtration. It is washed with water and recrystallized from chlorobenzene, giving a white solid: mp 193°-196°; 31P nmr (DMSO-d6) -14.0 ppm(d, J = 28Hz); 1H nmr δ8.8(d of d, 1, J = 2 and 11, NH), 6.8-7.8(m, 15, aryl), 5.2(d of d, 1, J = 10 and 25Hz, CH), 2.4(s, 6, CH3). cools to room temperature