4-(pyrrolidin-1-ylmethyl)aniline

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: A urea formation procedure similar to that used for the synthesis of ethyl 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-(4-(3-ethylureido)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate is used, utilizing 4-(pyrrolidin-1-ylmethyl)aniline as the aniline component. (52%, MS=553.5 (M+H))

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

Procedure: Prepared from 1-acetyl-3-(1-ethoxy-1-phenyl-methylidene)-5,6-dimethoxy-2-indolinone and 4-(pyrrolidin-1-yl-methyl)-aniline

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A small screw cap test tube was charged with 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid [3-(3-hydroxymethylene-2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide (as prepared in Example 69, 100 mg, 0.2401 mmol) and THF (3.0 mL). To the resulting solution was added 4-Pyrrolidin-1-ylmethyl-phenylamine (42.3 mg, 0.24 mmol), and the mixture was stirred for 24 h at 65° C. Subsequently, the reaction mixture was cooled to room temperature and diluted with EtOAc (˜5 mL) and Hexane (˜50 mL). The precipitate that formed was collected by filtration and washed with 0° C. iPrOH (˜5 mL) to afford the title compound in 25% yield (0.035 g, 0.0609 mmol). A small screw cap test tube Subsequently, the reaction mixture was cooled to room temperature The precipitate that formed was collected by filtration washed with 0° C. iPrOH (˜5 mL)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A small screw cap test tube was charged with 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid [3-(3-hydroxymethylene-2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide (as prepared in Example 69, 100 mg, 0.2401 mmol) and THF (3.0 mL). To the resulting solution was added 4-Pyrrolidin-1-ylmethyl-phenylamine (42.3 mg, 0.24 mmol), and the mixture was stirred for 24 h at 65° C. Subsequently, the reaction mixture was cooled to room temperature and diluted with EtOAc (˜5 mL) and Hexane (˜50 mL). The precipitate that formed was collected by filtration and washed with 0° C. iPrOH (˜5 mL) to afford the title compound in 25% yield (0.035 g, 0.0609 mmol). A small screw cap test tube Subsequently, the reaction mixture was cooled to room temperature The precipitate that formed was collected by filtration washed with 0° C. iPrOH (˜5 mL)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A small screw cap test tube was charged with N-[3-(3-Hydroxymethylene-2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-2-methyl-benzamide (prepared below, 100 mg, 0.251 mmol) and THF (2.5 mL). To the resulting solution was added 4-Pyrrolidin-1-ylmethyl-phenylamine (44.2 mg, 0.251 mmol), and the mixture was stirred for 24 h at 65° C. Subsequently, the reaction mixture was cooled to room temperature and diluted with EtOAc (˜5 mL) and Hexane (˜40 mL). The precipitate that formed was collected by filtration and washed with acetone (˜5 mL) to afford the title compound in 56% yield (0.078 g, 0.1401 mmol). A small screw cap test tube Subsequently, the reaction mixture was cooled to room temperature The precipitate that formed was collected by filtration washed with acetone (˜5 mL)