Ammonia → (1S,4R)-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 A (374 mg, 2.29 mmol) in dry DMF (3 mL) under N2 was added NaH (60% dispersion in oil, 183 mg, 4.58 mmol) and the resulting opaque brown solution was stirred at RT for 45 min (CARE: gas evolution). A solution of Intermediate 81c (537 mg, 2.29 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 AcOH (0.10 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 2-7% [2M NH3 in MeOH] in DCM, gave the title compound as a pale brown foam (505 mg, 58%). LCMS (Method 3): Rt 2.29 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 기록

ord-4ca60b6aee9a4e97b536f97083b44e21

출처 데이터셋

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08907094B2