Ammonia → (1S,4R)-4-[3-((R)-1-Methyl-pyrrolidin-3-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 (203 mg, 1.24 mmol) in dry DMF (3 mL) under N2 was added NaH (60% dispersion in oil, 83.0 mg, 2.07 mmol) (CARE: gas evolution) and the resulting opaque brown solution stirred at RT for 45 min. A solution of Intermediate 90d (228 mg, 1.03 mmol) in dry DMF (2 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 (2 mL) and AcOH (0.1 mL), applied to and SCX-2 cartridge (20 g) and washed with MeOH (75 mL). The product was eluted with 2M NH3 in MeOH (50 mL); concentration in vacuo gave a dark brown solid. FCC, using 5-15% (2M NH3 in MeOH) in DCM, gave the title compound as a light brown powder after freeze-drying (299 mg, 80%). LCMS (Method 3): Rt 0.44 min, m/z 364 [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 (2 mL)
4. washwashed with MeOH (75 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-d5fecb617960427f92ef9f4fb7955624

出典データセット

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08907094B2