(4S)-7-fluoro-3,4-dihydro-2H-chromen-4-amine;hydrochloride

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

Procedure: In a vial 3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine (101.0 mg, 0.216 mmol) and CDI (77 mg, 0.475 mmol) were dissolved in THF (6.00 ml) before treatment with 1.0 M solution NaHMDS in THF (0.454 ml, 0.454 mmol). After stirring at RT for 1 h, a solution of (S)-7-fluorochroman-4-amine hydrochloride (97 mg, 0.475 mmol) and TEA (0.151 ml, 1.080 mmol) in THF (2.00 ml) were added. The resulting mixture was heated to 55° C. for 1 h. The mixture was cooled to RT and taken up in DCM. The organic phase was washed with saturated NaHCO3 and the aqueous phase was back-extracted with DCM (2×). The combined organic layers were dried (Na2SO4) and volatiles were evaporated in vacuo. Crude material was purified via reverse phase HPLC over a gradient of 10-90% MeCN in water with 0.1% TFA to yield (S)-1-(7-fluorochroman-4-yl)-3-(3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (111 mg, 0.168 mmol, 78% yield). MS ESI calc'd. for C41H33FN6O6 [M+1]+ 661, found 661. The resulting mixture was heated to 55° C. for 1 h The mixture was cooled to RT The organic phase was washed with saturated NaHCO3 the aqueous phase was back-extracted with DCM (2×) The combined organic layers were dried (Na2SO4) and volatiles were evaporated in vacuo Crude material was purified via reverse phase HPLC over a gradient of 10-90% MeCN in water with 0.1% TFA

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

Procedure: In a vial 3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine (101.0 mg, 0.216 mmol) and CDI (77 mg, 0.475 mmol) were dissolved in THF (6.00 ml) before treatment with 1.0 M solution NaHMDS in THF (0.454 ml, 0.454 mmol). After stirring at RT for 1 h, a solution of (S)-7-fluorochroman-4-amine hydrochloride (97 mg, 0.475 mmol) and TEA (0.151 ml, 1.080 mmol) in THF (2.00 ml) were added. The resulting mixture was heated to 55° C. for 1 h. The mixture was cooled to RT and taken up in DCM. The organic phase was washed with saturated NaHCO3 and the aqueous phase was back-extracted with DCM (2×). The combined organic layers were dried (Na2SO4) and volatiles were evaporated in vacuo. Crude material was purified via reverse phase HPLC over a gradient of 10-90% MeCN in water with 0.1% TFA to yield (S)-1-(7-fluorochroman-4-yl)-3-(3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (111 mg, 0.168 mmol, 78% yield). MS ESI calc'd. for C41H33FN6O6 [M+1]+ 661, found 661. The resulting mixture was heated to 55° C. for 1 h The mixture was cooled to RT The organic phase was washed with saturated NaHCO3 the aqueous phase was back-extracted with DCM (2×) The combined organic layers were dried (Na2SO4) and volatiles were evaporated in vacuo Crude material was purified via reverse phase HPLC over a gradient of 10-90% MeCN in water with 0.1% TFA

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

Procedure: In a vial 3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine (101.0 mg, 0.216 mmol) and CDI (77 mg, 0.475 mmol) were dissolved in THF (6.00 ml) before treatment with 1.0 M solution NaHMDS in THF (0.454 ml, 0.454 mmol). After stirring at RT for 1 h, a solution of (S)-7-fluorochroman-4-amine hydrochloride (97 mg, 0.475 mmol) and TEA (0.151 ml, 1.080 mmol) in THF (2.00 ml) were added. The resulting mixture was heated to 55° C. for 1 h. The mixture was cooled to RT and taken up in DCM. The organic phase was washed with saturated NaHCO3 and the aqueous phase was back-extracted with DCM (2×). The combined organic layers were dried (Na2SO4) and volatiles were evaporated in vacuo. Crude material was purified via reverse phase HPLC over a gradient of 10-90% MeCN in water with 0.1% TFA to yield (S)-1-(7-fluorochroman-4-yl)-3-(3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (111 mg, 0.168 mmol, 78% yield). MS ESI calc'd. for C41H33FN6O6 [M+1]+ 661, found 661. The resulting mixture was heated to 55° C. for 1 h The mixture was cooled to RT The organic phase was washed with saturated NaHCO3 the aqueous phase was back-extracted with DCM (2×) The combined organic layers were dried (Na2SO4) and volatiles were evaporated in vacuo Crude material was purified via reverse phase HPLC over a gradient of 10-90% MeCN in water with 0.1% TFA