4-[(dimethylamino)methyl]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:; See reaction.notes.procedure_details.

Procedure: 3-(tert-Butoxycarbonylamino-methyl)-benzoic acid, (754 mg, 3.0 mmol), EDC (958.5 mg, 5.0 mmol), and HOBt (540.5 mg, 5.0 mmol) were combined in a reaction vial and DMF (5 mL) then N-methylmorpholine (0.549 mL, 5.0 mmol) were added. The reaction mixture was agitated for 1 h, then 4-dimethylaminomethyl-phenylamine (451 mg, 3 mmol) was added as a solution in 1 mL DMF. Shaking was continued 48 h. The reaction mixture was diluted to 50 mL with dichloromethane, washed with NaHCO3 (satd. aq., 1×25 mL, and brine (1×25 mL), dried and evaporated to a residue weighing approximately 2 g, which was taken up in 10 mL dichloromethane and treated with Si-isocyanate (silica-bound alkyl isocyanate; 1.2 g, 14.4 mmol). The resulting mixture was agitated overnight and the silica reagent was filtered. The filtrate was evaporated to provide the intermediate ([3-(4-dimethylaminomethyl-phenylcarbamoyl)-benzyl]-carbamic acid tert-butyl ester), which was treated directly with a solution of TFA (2 mL) in dichloromethane (5 mL). The reaction mixture was stirred for 2 h, then the solvents were evaporated and the residue was re-dissolved in dichloromethane (25 mL). This solution was washed with NaHCO3 (satd. aq., 1×25 mL). To this wash was added 1 g Na2CO3 and the wash was extracted with dichloromethane (2×25 mL). The organic extracts were combined and washed with brine (1×25 mL), dried and evaporated to 160 mg of a solid (3-aminomethyl-N-(4-dimethylaminomethyl-phenyl)-benzamide-20%-2 steps) which was used directly. This intermediate (28.3 mg, 0.1 mmol) was dissolved in DMF (1 mL), and 4-isocyanato-1,2-dimethoxy-benzene (23.3 mg, 0.13 mmol) was added. The resulting mixture was agitated for 48 hours, then was purified directly by preparative HPLC using an acetonitrile/water/formic acid gradient. The title compound was collected as a formate salt (31 mg, 67% yield), MS analysis electrospray, 426 (M+H). Shaking was continued 48 h washed with NaHCO3 (satd aq., 1×25 mL, and brine (1×25 mL), dried evaporated to a residue The resulting mixture was agitated overnight the silica reagent was filtered The filtrate was evaporated

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

Procedure: 200 mg (0.57 mmol) 1,5-diacetyl-3-[ethoxy-phenyl-methylidene]-2-indolinone (Ex. III) are suspended in 5 ml of dimethylformamide and stirred with 86 mg 0.57 mmol) 4-dimethylaminomethyl-phenylamine at an ambient temperature of 80° C. for about 5 h. The acetyl-protected intermediate product is combined with 2 ml of conc. ammonia without being purified and stirred overnight at ambient temperature. Then the mixture is evaporated down and the residue is chromatographed through a silica gel column with methylene chloride/methanol 9:1 as eluant. without being purified Then the mixture is evaporated down the residue is chromatographed through a silica gel column with methylene chloride/methanol 9:1 as eluant

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-((dimethylamino)methyl)aniline as the aniline component. (23%, MS=527.2 (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)-6-(2-tolyl)-2-indolinone and 4-(dimethylaminomethyl)-aniline

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

Procedure: Prepared from 3-(1-methoxy-1-phenyl-methylidene)-5,6-methylenedioxy-2-indolinone and 4-(dimethylaminomethyl)-aniline

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

Procedure: Prepared from 3-(1-methoxy-1-phenyl-methylidene)-5,6-methylenedioxy-2-indolinone and 4-(dimethylaminomethyl)-aniline

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

Procedure: Prepared from 1-acetyl-3-(1-ethoxy-1-ethyl-methylidene)-5,6-dimethoxy-2-indolinone and 4-(dimethylaminomethyl)-aniline

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-(dimethylaminomethyl)-aniline