2-methyl-1-(methylamino)propan-2-ol

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

Procedure: HATU coupling of 1-(5-(2-fluorophenyl)pyrimidin-2-yl)-3-(methylsulfinyl)-1H-indole-6-carboxylic acid with 2-methyl-1-(methylamino)propan-2-ol. White solid. Yield: 110 mg

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1-methyl-4-nitro-1H-pyrazole-3-carboxylic acid (639 mg, 3.7 mmol) and 2-methyl-1-(methylamino)propan-2-ol (500 mg, 4.85 mmol) in THF (15 mL) were added HATU (1.57 g, 4.12 mmol) and N-methylmorpholine (2.13 mL, 19.4 mmol) at ambient temperature. The mixture was heated to 70° C. and stirred for 16 h. After cooling down to ambient temperature, the reaction mixture was poured into 20 mL HCl (2N aqueous solution) and extracted with ethyl acetate (2×100 mL). The organic layers were washed with water, brine and the solvent was evaporated. The aqueous layer was back-extracted with dichloromethane, dried and concentrated in vacuo. Both residues were combined to give 2.75 g of a semi-solid yellow material. The crude material was purified by silica gel chromatography using a methanol/ethyl acetate gradient to yield the product (1.2 g, 90%) as colorless oil. After cooling down to ambient temperature extracted with ethyl acetate (2×100 mL) The organic layers were washed with water, brine the solvent was evaporated The aqueous layer was back-extracted with dichloromethane dried concentrated in vacuo

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1-methyl-4-nitro-1H-pyrazole-3-carboxylic acid (639 mg, 3.7 mmol) and 2-methyl-1-(methylamino)propan-2-ol (500 mg, 4.85 mmol) in THF (15 mL) were added HATU (1.57 g, 4.12 mmol) and N-methylmorpholine (2.13 mL, 19.4 mmol) at ambient temperature. The mixture was heated to 70° C. and stirred for 16 h. After cooling down to ambient temperature, the reaction mixture was poured into 20 mL HCl (2N aqueous solution) and extracted with ethyl acetate (2×100 mL). The organic layers were washed with water, brine and the solvent was evaporated. The aqueous layer was back-extracted with dichloromethane, dried and concentrated in vacuo. Both residues were combined to give 2.75 g of a semi-solid yellow material. The crude material was purified by silica gel chromatography using a methanol/ethyl acetate gradient to yield the product (1.2 g, 90%) as colorless oil. After cooling down to ambient temperature extracted with ethyl acetate (2×100 mL) The organic layers were washed with water, brine the solvent was evaporated The aqueous layer was back-extracted with dichloromethane dried concentrated in vacuo

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1-methyl-4-nitro-1H-pyrazole-3-carboxylic acid (639 mg, 3.7 mmol) and 2-methyl-1-(methylamino)propan-2-ol (500 mg, 4.85 mmol) in THF (15 mL) were added HATU (1.57 g, 4.12 mmol) and N-methylmorpholine (2.13 mL, 19.4 mmol) at ambient temperature. The mixture was heated to 70° C. and stirred for 16 h. After cooling down to ambient temperature, the reaction mixture was poured into 20 mL HCl (2N aqueous solution) and extracted with ethyl acetate (2×100 mL). The organic layers were washed with water, brine and the solvent was evaporated. The aqueous layer was back-extracted with dichloromethane, dried and concentrated in vacuo. Both residues were combined to give 2.75 g of a semi-solid yellow material. The crude material was purified by silica gel chromatography using a methanol/ethyl acetate gradient to yield the product (1.2 g, 90%) as colorless oil. After cooling down to ambient temperature extracted with ethyl acetate (2×100 mL) The organic layers were washed with water, brine the solvent was evaporated The aqueous layer was back-extracted with dichloromethane dried concentrated in vacuo

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1-methyl-4-nitro-1H-pyrazole-3-carboxylic acid (639 mg, 3.7 mmol) and 2-methyl-1-(methylamino)propan-2-ol (500 mg, 4.85 mmol) in THF (15 mL) were added HATU (1.57 g, 4.12 mmol) and N-methylmorpholine (2.13 mL, 19.4 mmol) at ambient temperature. The mixture was heated to 70° C. and stirred for 16 h. After cooling down to ambient temperature, the reaction mixture was poured into 20 mL HCl (2N aqueous solution) and extracted with ethyl acetate (2×100 mL). The organic layers were washed with water, brine and the solvent was evaporated. The aqueous layer was back-extracted with dichloromethane, dried and concentrated in vacuo. Both residues were combined to give 2.75 g of a semi-solid yellow material. The crude material was purified by silica gel chromatography using a methanol/ethyl acetate gradient to yield the product (1.2 g, 90%) as colorless oil. After cooling down to ambient temperature extracted with ethyl acetate (2×100 mL) The organic layers were washed with water, brine the solvent was evaporated The aqueous layer was back-extracted with dichloromethane dried concentrated in vacuo

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

Procedure: HATU coupling of 1-(5-(2-fluorophenyl)pyrimidin-2-yl)-3-(methylsulfinyl)-1H-indole-6-carboxylic acid with 2-methyl-1-(methylamino)propan-2-ol. White solid. Yield: 110 mg

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1-methyl-4-nitro-1H-pyrazole-3-carboxylic acid (639 mg, 3.7 mmol) and 2-methyl-1-(methylamino)propan-2-ol (500 mg, 4.85 mmol) in THF (15 mL) were added HATU (1.57 g, 4.12 mmol) and N-methylmorpholine (2.13 mL, 19.4 mmol) at ambient temperature. The mixture was heated to 70° C. and stirred for 16 h. After cooling down to ambient temperature, the reaction mixture was poured into 20 mL HCl (2N aqueous solution) and extracted with ethyl acetate (2×100 mL). The organic layers were washed with water, brine and the solvent was evaporated. The aqueous layer was back-extracted with dichloromethane, dried and concentrated in vacuo. Both residues were combined to give 2.75 g of a semi-solid yellow material. The crude material was purified by silica gel chromatography using a methanol/ethyl acetate gradient to yield the product (1.2 g, 90%) as colorless oil. After cooling down to ambient temperature extracted with ethyl acetate (2×100 mL) The organic layers were washed with water, brine the solvent was evaporated The aqueous layer was back-extracted with dichloromethane dried concentrated in vacuo