Reaktion #612088

Reaktionsgleichung

1-[[1-(3-chloro-5-fluoro-4-pyridyl)-4-piperidyl]sulfonyl]-4-methyl-piperazine

TFA

Tert-butyl carbamate

sodium tert-butoxide

BrettPhos

→

5-fluoro-4-(4-((4-methylpiperazin-1-yl)sulfonyl)piperidin-1-yl)pyridin-3-amine

Lösungsmittel

DCM

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter 5 minutes at 80° C. the reaction was cooled to RT
2. 2
   Sonstigepartitioned between ethyl acetate and water
3. 3
   TrocknenThe combined organics was dried with MgSO4
4. 4
   Einengenconcentrated in vacuo to a yellow solid
5. 5
   SonstigeThe yellow solid was purified by column chromatography
6. 6
   Waschento elute side products
7. 7
   Waschen5-10% MeOH/DCM to elute product
8. 8
   Einengenconcentrated in vacuo
9. 9
   Sonstigeto yield a light yellow solid
10. 10
    EinengenThe mixture was concentrated in vacuo

Vorschrift

Tert-butyl carbamate (211.3 mg, 1.804 mmol), sodium tert-butoxide (173.4 mg, 1.804 mmol), BrettPhos Pre-catalyst (143.7 mg, 0.1804 mmol) and BrettPhos (96.83 mg, 0.1804 mmol) were degassed by vacuum/nitrogen cycles (×5). A solution of 1-[[1-(3-chloro-5-fluoro-4-pyridyl)-4-piperidyl]sulfonyl]-4-methyl-piperazine (340 mg, 0.9022 mmol) in dry toluene (9.884 mL) was added and the resulting mixture was heated to 80° C. After 5 minutes at 80° C. the reaction was cooled to RT and partitioned between ethyl acetate and water. The combined organics was dried with MgSO4 and concentrated in vacuo to a yellow solid. The yellow solid was purified by column chromatography using 1% MeOH/DCM to elute side products and then 5-10% MeOH/DCM to elute product. Relevant fractions combined and concentrated in vacuo to yield a light yellow solid. It was dissolved in DCM (10 mL) followed by the addition of TFA (1.029 g, 695.3 μL, 9.022 mmol). The mixture was stirred at room temperature for 2 hours. The mixture was concentrated in vacuo to yield 5-fluoro-4-(4-((4-methylpiperazin-1-yl)sulfonyl)piperidin-1-yl)pyridin-3-amine as a light orange solid. MS (ES+) 358.1.

Quelle