Reaktion #306359

Reaktionsgleichung

1-(2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanol

N-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-methoxy-1,5-naphthyridin-4-amine

cesium carbonate

→

1-(2-chloro-4-(3-((7-methoxy-1,5-naphthyridin-4-ylamino)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)ethanol

Lösungsmittel

dioxane

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas sparged with argon for 5 min
2. 2
   SonstigeReaction
3. 3
   Temperaturcooled
4. 4
   Sonstigethen partitioned between 9:1 CHCl3/IPA (20 mL) and 1M NaOH (15 mL)
5. 5
   ExtraktionAqueous further extracted with 9:1 CHCl3/IPA (2×10 mL)
6. 6
   TrocknenThe combined organics dried over MgSO4
7. 7
   Einengenconcentrated
8. 8
   Sonstigepurified on 40 g silica eluting with an isocratic 7% 2M NH3 in MeOH/DCM
9. 9
   WaschenProduct further purified prep HPLC eluting with water/ACN (0.1% TFA)
10. 10
    SonstigeAfter collected fractions
11. 11
    workup.DISSOLUTIONwas dissolved in 1:1 ACN/water
12. 12
    SonstigeResulting solid
13. 13
    Sonstigecollected by filteration and solid
14. 14
    Waschenwashed with water (2 mL)

Vorschrift

A suspension of 1-(2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanol (228 mg, 807 μmol), N-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-methoxy-1,5-naphthyridin-4-amine (197 mg, 576 μmol), dichloro[1,1′bis(diphenylphoshino)ferrocene]palladium(ii) dichloromethane adduct (127 mg, 173 μmol), cesium carbonate (751 mg, 2306 μmol) in dioxane (3 mL) and water (0.6 mL) was sparged with argon for 5 min then heated to 100° C. for 6 h. Reaction cooled then partitioned between 9:1 CHCl3/IPA (20 mL) and 1M NaOH (15 mL). Aqueous further extracted with 9:1 CHCl3/IPA (2×10 mL). The combined organics dried over MgSO4. concentrated, then purified on 40 g silica eluting with an isocratic 7% 2M NH3 in MeOH/DCM. Product further purified prep HPLC eluting with water/ACN (0.1% TFA). After collected fractions were reduced to a clear the residue was dissolved in 1:1 ACN/water and pH adjusted to 9 with 1M NaOH (3-4 drops). Resulting solid collected by filteration and solid washed with water (2 mL). MS (ESI pos. ion) m/z: 462 (MH+). Calc'd exact mass for C23H20ClN7O2: 461.

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