Ammonia → (1S,4S)-4-[3-((S)-2-Methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

To a solution of Intermediate B (232 mg, 1.6 mmol) in dry DMF (10 mL) under N2 was added sodium (60% dispersion in oil, 320 mg, 8.0 mmol) and the resulting opaque brown solution was stirred at RT for 45 min (CARE: gas evolution). A solution of Intermediate 81c (342 mg, 1.46 mmol) in dry DMF (7 mL) was added and the dark brown solution stirred at 60° C. under N2 for 90 min. The cooled solution was concentrated in vacuo, redissolved in MeOH (3 mL) and then applied to an SCX-2 cartridge (20 g), washing with MeOH (50 mL). The product was eluted with 2M NH3 in MeOH (50 mL); concentration in vacuo gave a dark brown solid. FCC, using 0-10% [2M NH3 in MeOH] in DCM, gave the title compound as a pale brown foam (262 mg, 45%). LCMS (Method 3): Rt 2.30 min, m/z 378 [MH+].

1. stirringthe dark brown solution stirred at 60° C. under N2 for 90 min
2. concentrationThe cooled solution was concentrated in vacuo
3. dissolutionredissolved in MeOH (3 mL)
4. washwashing with MeOH (50 mL)
5. washThe product was eluted with 2M NH3 in MeOH (50 mL)
6. concentrationconcentration in vacuo
7. customgave a dark brown solid

ORDレコード

ord-b9fa1b01c3664b48a3822bd9b64578fb

出典データセット

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09315503B2