Acetic Acid → (1S,4R)-4-[3-(4-Allyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

A suspension of Intermediate A (108 mg, 0.661 mmol) and NaH (60% dispersion in oil, 72.1 mg, 180 mmol) in dry DMF (5 mL) at RT under Ar was stirred for 1 h (CARE: gas evolution). A solution of Intermediate 57a (166 mg, 0.601 mmol) in dry DMF (3 mL) was added and the dark brown solution stirred at 60° C. for 90 min. The solution was concentrated in vacuo, and the residue redissolved in MeOH (5 mL) and AcOH (0.171 mL, 3.00 mmol). The solution was applied to an SCX-2 cartridge (10 g) and was washed with MeOH (100 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo left a dark brown solid. FCC, using 2-8% [2M NH3 in MeOH] in DCM, gave the title compound as a dark brown oil (204 mg, 81%). LCMS (Method 3): Rt 2.34 min, m/z 420 [MH+].

1. stirringthe dark brown solution stirred at 60° C. for 90 min
2. concentrationThe solution was concentrated in vacuo
3. dissolutionthe residue redissolved in MeOH (5 mL)
4. washwas washed with MeOH (100 mL)
5. washThe product was eluted with 2M NH3 in MeOH (75 mL)
6. concentrationconcentration in vacuo
7. waitleft a dark brown solid

ORDレコード

ord-dc44924121a048c0800ef5417df6b232

出典データセット

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08907094B2