Reaktion #88934

Reaktionsgleichung

Intermediate 61d

[5-tert-Butyl-2-(3-hydroxymethyl-4-triisopropylsilanyloxy-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

Intermediate B

(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

DIPEA

→

title compound

Ausbeute 58.0%

1-[5-tert-Butyl-2-(3-hydroxymethyl-4-triisopropylsilanyloxy-phenyl)-2H-pyrazol-3-yl]-3-{(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-yl}-urea

Ausbeute 58.0%

Lösungsmittel

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was evaporated in vacuo
2. 2
   Sonstigethe residue was partitioned between DCM and water
3. 3
   ExtraktionThe aqueous layer was then extracted with DCM (2×)
4. 4
   WaschenThe combined organic layers were washed with brine
5. 5
   Trocknendried (Na2SO4)
6. 6
   Filtrationfiltered
7. 7
   Sonstigeevaporated in vacuo
8. 8
   SonstigeThe residue was purified by FCC

Vorschrift

A solution of Intermediate 61d (173 mg, 0.29 mmol), Intermediate B (100 mg, 0.27 mmol) and DIPEA (58 μL, 0.33 mmol) in 1,4-dioxane (2.9 mL) was stirred at 70° C. for 42 h. The mixture was evaporated in vacuo and the residue was partitioned between DCM and water. The aqueous layer was then extracted with DCM (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-5% MeOH in DCM, to give the title compound as a cream colored glass (127 mg, 58%). LCMS (Method 3): Rt 4.97 min, m/z 821 [MH+].

Quelle