Reaktion #718096

Reaktionsgleichung

Intermediate 120b

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

sodium hydride

Intermediate A

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

→

title compound

Ausbeute 45.3%

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

Ausbeute 45.3%

Lösungsmittel

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling
2. 2
   Sonstigethe reaction mixture was quenched by careful addition of MeOH
3. 3
   WaschenThe cartridge was washed with MeOH
4. 4
   Waschenthe product eluted with 2M NH3 in MeOH
5. 5
   workup.ADDITIONThe product containing fractions
6. 6
   Einengenwere concentrated in vacuo
7. 7
   Sonstigethe resultant residue was purified by FCC on silica

Vorschrift

To a suspension of sodium hydride (60% in mineral oil, 54 mg, 1.34 mmol) in DMF (1 mL) was added Intermediate A (88 mg, 0.54 mmol) and the reaction mixture was stirred for 20 min. A solution of Intermediate 120b (105 mg, 0.45 mmol) in DMF (1 mL) was added and the reaction mixture was heated at 60° C. for 90 min. After cooling, the reaction mixture was quenched by careful addition of MeOH and then loaded onto an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH. The product containing fractions were concentrated in vacuo and the resultant residue was purified by FCC on silica, using a gradient of 0-10% [2M NH3 in MeOH] in DCM, to give the title compound (77 mg, 45%). 1H NMR (400 MHz, CDCl3): 1.38-1.51 (1H, m), 1.52-1.90 (6H, m), 1.90-2.05 (1H, m), 2.03 (3H, s), 2.04-2.15 (1H, m), 2.15-2.22 (1H, m), 2.33-2.44 (1H, m), 2.99-3.06 (1H, m), 3.82 (1H, dd, J=11.3, 3.2 Hz), 3.99 (1H, dd, J=7.9, 5.1 Hz), 5.23 (1H, t, J=4.5 Hz), 7.11 (1H, dd, J=9.9, 2.2 Hz), 7.23-7.30 (1H, m), 7.34-7.41 (2H, m), 7.60 (1H, d, J=7.7 Hz), 7.65 (1H, dd, J=9.9, 0.7 Hz), 8.42 (1H, d, J=2.2 Hz).

Quelle