2-methylmorpholine;hydrochloride

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

Procedure: The solution of (S)-[1-(3-bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester (4.36 g, 14.5 mmol), 2-Methyl-morpholine hydrochloric acid salt (4 g. 2eq.), palladium acetate (20 mol %, 652 mg), 2-(di-t-butylphosphino) biphenyl (40 mol %, 1.73 g), triethylamine (4.45 ml, 2.2eq.), and sodium tert-butoxide (1.54 g, 1.1eq) in toluene (26 ml) was stirred at 80° C. for 2 days. The solution was filtered through Celite Pad and washed with ethyl acetate. The filtrate was washed with saturated sodium bicarbonate solution and the organic layer was separated. The aqueous layer was extracted with ethyl acetate three times. The combined organic layer was dried over magnesium sulfate and concentrated under vacuum. The crude product was purified by flash chromatography with 25% ethyl acetate/hexane. Yellow sticky oil was obtained as the product (2.7 g, 58% yield). The solution was filtered through Celite Pad washed with ethyl acetate The filtrate was washed with saturated sodium bicarbonate solution the organic layer was separated The aqueous layer was extracted with ethyl acetate three times The combined organic layer was dried over magnesium sulfate concentrated under vacuum The crude product was purified by flash chromatography with 25% ethyl acetate/hexane

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

Procedure: The solution of (S)-[1-(3-bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester (4.36 g, 14.5 mmol), 2-Methyl-morpholine hydrochloric acid salt (4 g. 2eq.), palladium acetate (20 mol %, 652 mg), 2-(di-t-butylphosphino) biphenyl (40 mol %, 1.73 g), triethylamine (4.45 ml, 2.2eq.), and sodium tert-butoxide (1.54 g, 1.1eq) in toluene (26 ml) was stirred at 80° C. for 2 days. The solution was filtered through Celite Pad and washed with ethyl acetate. The filtrate was washed with saturated sodium bicarbonate solution and the organic layer was separated. The aqueous layer was extracted with ethyl acetate three times. The combined organic layer was dried over magnesium sulfate and concentrated under vacuum. The crude product was purified by flash chromatography with 25% ethyl acetate/hexane. Yellow sticky oil was obtained as the product (2.7 g, 58% yield). The solution was filtered through Celite Pad washed with ethyl acetate The filtrate was washed with saturated sodium bicarbonate solution the organic layer was separated The aqueous layer was extracted with ethyl acetate three times The combined organic layer was dried over magnesium sulfate concentrated under vacuum The crude product was purified by flash chromatography with 25% ethyl acetate/hexane

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of triethylamine (2 drops), 2-methylmorpholine hydrochloride (16 mg, 0.154 mmol) and 4-(2,3-dichlorobenzyl)-2-(methylsulfonyl)thiazolo[4,5-d]pyrimidin-7(4H)-one (20 mg, 0.051 mmol) in DMF was stirred at 60° C. for 1 h. After cooled to ambient temperature, the mixture was diluted with water (10 mL) and extracted with dichloromethane (15 mL×3). The combined organic layers were washed with saturated brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (DCM:MeOH=20:1 elution) to give the desired product (8 mg, 38%) as a white solid. 1H NMR (300 MHz, d6-DMSO) δ 8.49 (s, 1H), 7.63 (d, J=7.2 Hz, 1H), 7.35 (d, J=7.8 Hz, 1H), 7.16 (s, J=6.9 Hz, 1H), 5.46 (s, 2H), 3.88 (dd, J=12.3, 2.7 Hz, 1H), 3.77 (br, 2H), 3.55-3.47 (m, 2H), 3.31-3.20 (m, 1H), 2.94-2.89 (m. 1H), 1.13 (d, J=5.7 Hz, 3H); LC-MS: 411 (MH+); IR (thin film): 2976, 2920, 2855, 2360, 1627, 1605, 1555, 1495, 1444 cm−1. After cooled to ambient temperature extracted with dichloromethane (15 mL×3) The combined organic layers were washed with saturated brine dried over anhydrous Na2SO4 filtered concentrated in vacuo The residue was purified by flash column chromatography on silica gel (DCM:MeOH=20:1 elution)

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

Procedure: A mixture of 2-methylmorpholine hydrochloride (1.0 g, 9.9 mmol), dimethyl cyanocarbonimidodithioate (1.45 g, 9.9 mmol) and sodium carbonate (0.2 g, 1.9 mmol) in ethanol (50 mL) was stirred at ambient temperature overnight. The reaction mixture was concentrated and purified through silica gel chromatography to give the desired product (1.25 g, 63%). LC-MS: 200 (MH+). The reaction mixture was concentrated purified through silica gel chromatography