Reaktion #309489

Reaktionsgleichung

tert-Butyl 4-[2-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-2-hydroxyethyl]piperazine-1-carboxylate

1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

potassium fluoride

→

title compound

tert-butyl 4-{2-hydroxy-2-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]ethyl}piperazine-1-carboxylate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewhich was evacuated
2. 2
   workup.ADDITIONFully degassed DMF (1.5 mL) was added
3. 3
   SonstigeThe tube was placed in an oil bath at 115° C.
4. 4
   workup.ADDITIONThe reaction mixture was poured into an ethyl acetate/brine mixture
5. 5
   Extraktionextracted with ethyl acetate
6. 6
   TrocknenCombined organics were dried over magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated in vacuo
9. 9
   Sonstigepurified via reverse phase HPLC (10-42% acetonitrile/water gradient, 0.05% trifluoroacetic acid modifier)

Vorschrift

tert-Butyl 4-[2-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-2-hydroxyethyl]piperazine-1-carboxylate (65 mg, 0.138 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (58 mg, 0.28 mol), Pd2(dba)3 (6 mg, 0.007 mmol), (tBu3)PBF4 (4 mg, 0.014 mmol), and potassium fluoride (27 mg, 0.46 mmol) were combined in a sealed tube which was evacuated and backfilled with argon three times. Fully degassed DMF (1.5 mL) was added. The tube was placed in an oil bath at 115° C. and stirred for 19 hours. The reaction mixture was poured into an ethyl acetate/brine mixture and extracted with ethyl acetate. Combined organics were dried over magnesium sulfate, filtered, concentrated in vacuo, and purified via reverse phase HPLC (10-42% acetonitrile/water gradient, 0.05% trifluoroacetic acid modifier) to afford the title compound. 1H NMR (600 MHz, CDCl3) δ 9.00 (d, 1H); 8.55 (d, 1H); 8.23 (d, 1H); 7.91 (s, 1H); 7.80 (s, 1H); 7.76 (dd, 1H); 7.60 (d, 1H); 7.34 (d, 1H); 7.23 (d, 1H); 4.95 (d, 1H); 3.98 (s, 3H); 3.56-3.51 (m, 4H); 2.78-2.53 (m, 6H); 1.46 (s, 9H). Hydroxyl proton was not observed. LRMS (APCI) calc'd for (C29H34N5O4) [M+H]+, 516.3; found 516.3.

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