Reaktion #718029

Reaktionsgleichung

Intermediate 88d

6-Fluoro-3-((S)-1-methyl-piperidin-3-yl)-[1,2,4]triazolo[4,3-a]pyridine

Intermediate A

(1R,4S)-4-Amino-1,2,3,4-tetrahydro-naphthalen-1-ol

NaH

→

title compound

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

Lösungsmittel

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe resulting dark brown solution stirred at 60° C. for 90 min
2. 2
   EinengenThe cooled solution was concentrated in vacuo
3. 3
   workup.DISSOLUTIONredissolved in MeOH (2 mL)
4. 4
   Waschenwashed with MeOH (75 mL)
5. 5
   WaschenThe product was eluted with 2M NH3 in MeOH (60 mL)
6. 6
   Einengenconcentration in vacuo
7. 7
   workup.WAITleft a dark brown solid

Vorschrift

To a solution of Intermediate A (196 mg, 1.20 mmol) in dry DMF (3 mL) at RT under N2 was added NaH (60% dispersion in oil, 80 mg, 2.00 mmol) and the resulting opaque brown solution stirred for 45 min. A solution of Intermediate 88d (234 mg, 1.00 mmol) in dry DMF (2 mL) was added and the resulting dark brown solution stirred at 60° C. 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 and washed with MeOH (75 mL). The product was eluted with 2M NH3 in MeOH (60 mL); concentration in vacuo left a dark brown solid. FCC, using 3-13% [2M NH3 in MeOH] in DCM, gave the title compound as a light brown solid after freeze-drying (280 mg, 74%). LCMS (Method 3): Rt 0.44 min, m/z 378 [MH+].

Quelle