1-cyclopropylethanamine

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: Synthesized according to the method of reagent preparation 46 by first conducting step 2 to give a mixture of ethyl 3-bromo-2-chloro-4-cyanobenzoate and ethyl 5-bromo-2-chloro-4-cyanobenzoate then proceeding with step 1 using 1-cyclopropylethylamine followed by steps 3 and 4. 1HNMR (400 MHz, CD3OD): 7.49 (d, 1H), 7.22 (d, 1H), 2.84 (q, 2H), 1.17 (d, 3H), 0.9-0.76 (m, 1H), 0.3-0.26 (m, 2H), 0.04-0.00 (m, 2H). MS (EI) for C13H15ClN2O3: 284 (MH+). Synthesized according to the method of reagent preparation 46 to give

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

Procedure: Synthesized according to the method of reagent preparation 46 by first conducting step 2 to give a mixture of ethyl 3-bromo-2-chloro-4-cyanobenzoate and ethyl 5-bromo-2-chloro-4-cyanobenzoate then proceeding with step 1 using 1-cyclopropylethylamine followed by steps 3 and 4. 1HNMR (400 MHz, CD3OD): 7.49 (d, 1H), 7.22 (d, 1H), 2.84 (q, 2H), 1.17 (d, 3H), 0.9-0.76 (m, 1H), 0.3-0.26 (m, 2H), 0.04-0.00 (m, 2H). MS (EI) for C13H15ClN2O3: 284 (MH+). Synthesized according to the method of reagent preparation 46 to give

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11.2 g (0.132 mol) of 1-cyclopropylethylamine were added to a mixture of 22.3 g (0.115 mol) of 5-nitropyridine-2,3-dicarboxylic anhydride in 150 ml of 1,2-dichloroethane at 25a° C with stirring in the course of 8 minutes and the mixture was stirred at 70° C. for 3 hours. After cooling to 25° C., 19.6 g (0.165 mol) of thionyl chloride were added with stirring in the course of 10 minutes and the mixture was stirred at 25° C. for 10 hours and at 70° C for 11/2 hours. The reaction mixture was diluted with 100 ml of methylene chloride and added with stirring to 500 ml of ice-water. The aqueous phase was extracted twice more with methylene chloride. The organic phase was then washed successively with water, saturated sodium hydrogencarbonate and sodium chloride solution and filtered off with suction over neutral alumina. After concentrating, 21.5 g (72% of theory) of the title compound of m.p. 96-99° C. were obtained (active compound Example 1.020). the mixture was stirred at 70° C. for 3 hours with stirring in the course of 10 minutes the mixture was stirred at 25° C. for 10 hours and at 70° C for 11/2 hours added The aqueous phase was extracted twice more with methylene chloride The organic phase was then washed successively with water, saturated sodium hydrogencarbonate and sodium chloride solution filtered off with suction over neutral alumina After concentrating

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

Procedure: 1-Chloro-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrile (400 mg, 1.63 mmol), 1-cyclopropylethanamine (594 mg, 4.89 mmol), Pd2(dba)3 (74.6 mg, 0.081 mmol), BINAP (152 mg, 0.24 mmol), and sodium tert-butoxide (782 mg, 8.14 mmol) were placed in a sealed tube. The mixture was evacuated and backfilled with argon three times. Fully degassed DME (8.1 ml) was added. The tube was sealed and the reaction was heated to 85° C. and stirred for 20 hrs. The reaction was cooled to ambient temperature, concentrated in vacuo, and directly purified via flash chromatography to afford the title compound. LRMS (APCI) calc'd for (C17H16FN4) [M+H]+, 295.1. found 295.0. The mixture was evacuated Fully degassed DME (8.1 ml) was added The tube was sealed The reaction was cooled to ambient temperature concentrated in vacuo directly purified via flash chromatography

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11.2 g (0.132 mol) of 1-cyclopropylethylamine were added to a mixture of 22.3 g (0.115 mol) of 5-nitropyridine-2,3-dicarboxylic anhydride in 150 ml of 1,2-dichloroethane at 25° C. with stirring in the course of 8 minutes and the mixture was stirred at 70° C. for 3 hours. After cooling to 25° C., 19.6 g (0.165 mol) of thionyl chloride were added with stirring in the course of 10 minutes and the mixture was stirred at 25° C. for 10 hours and at 70° C. for 1 1/2 hours. The reaction mixture was diluted with 100 ml of methylene chloride and added with stirring to 500 ml of ice-water. The aqueous phase was extracted twice more with methylene chloride. The organic phase was then washed successively with water, saturated sodium hydrogencarbonate and sodium chloride solution and filtered off with suction over neutral alumina. After concentrating, 21.5 g (72% of theory) of the title compound of m.p. 96°-99° C. were obtained (active compound Example 1.020). the mixture was stirred at 70° C. for 3 hours with stirring in the course of 10 minutes the mixture was stirred at 25° C. for 10 hours and at 70° C. for 1 1/2 hours added The aqueous phase was extracted twice more with methylene chloride The organic phase was then washed successively with water, saturated sodium hydrogencarbonate and sodium chloride solution filtered off with suction over neutral alumina After concentrating

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

Procedure: Following the procedure as described in Example 1, making variations only as required to use 2-(4-hydroxy-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxylic acid in place of 4-methyl-2-(2-oxo-4-phenylpyridin-1(2H)-yl)thiazole-5-carboxylic acid to react with cyclopropylethanamine, the title compound was obtained as a colorless solid in 76% yield: mp 240-242° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, DMSO-d6) δ 11.56 (br s, 1H), 8.58 (d, J=8.0 Hz, 1H), 8.26 (t, J=5.6 Hz, 1H), 6.25 (dd, J=8.0, 2.5 Hz, 1H), 5.81 (d, J=2.5 Hz, 1H), 3.05 (m, 2H), 2.51 (s, 3H), 1.05-0.92 (m, 1H), 0.43-0.36 (m, 2H), 0.20-0.15 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 167.9, 161.8, 161.6, 153.9, 149.7, 132.6, 124.0, 104.3, 98.0, 43.9, 17.4, 11.4, 3.7; MS (ES+) m/z: 306.2 (M+1).