Potassium Carbonate → tert-butyl 4-(1H-indazol-5-yl)-3,6-dihydropyridine-1(2H)-carboxylate

Temperature

90 °C

A suspension of 5-bromoindazole (Combi-blocks; 3.0 g; 15.2 mmol; 1.0 eq.), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (Frontier Scientific; 6.59 g; 21.3 mmol; 1.4 eq.), 1,1′-bis-(diphenylphosphino)ferrocene (1.11 g; 1.52 mmol; 0.1 eq.) and potassium carbonate (6.31 g; 45.7 mmol; 3.0 eq.) in degassed dioxane (60 mL) and water (30 mL) was heated at 90° C. for 24 h. The reaction mixture was cooled, diluted with DCM and filtered through a celite pad. Water was added to the filtrate and aqueous phase was extracted three times with DCM. Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude was adsorbed on silica and purified by flash chromatography on silica (heptane/EtOAc, gradient from 80:20 to 30:70) to give the title compound as an off white solid. 1H NMR (300 MHz, DMSO-d6) δ 13.04 (brs, 1H), 8.04 (s, 1H), 7.78-7.71 (m, 1H), 7.53-7.44 (m, 2H), 6.14 (s, 1H), 4.10-3.92 (m, 2H), 3.56 (t, J=5.7 Hz, 2H), 2.60-2.51 (m, 2H), 1.41 (s, 9H). HPLC (Condition A): Rt 4.42 min (purity 93.6%). MS (ES+): 341.2. MS (ES−): 298.2.

1. temperatureThe reaction mixture was cooled
2. filtrationfiltered through a celite pad
3. additionWater was added to the filtrate and aqueous phase
4. extractionwas extracted three times with DCM
5. washCombined organic phases were washed with brine
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. custompurified by flash chromatography on silica (heptane/EtOAc, gradient from 80:20 to 30:70)

ORD record

ord-671006119fef4c48b8112778fd1e0fce

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073892B2