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

HRID 1520015Notes

Reaction equation

HRID 1520015 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.CC1(C)C(C)(C)OB([C:19]2[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:23][CH:24]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[NH:7]1[C:8]2[C:4](=[CH:3][C:2]([C:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]=3)=[CH:10][CH:9]=2)[CH:5]=[N:6]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 7619295-bromo-1H-indazoleHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 67981587tert-butyl 4-(1H-indazol-5-yl)-3,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-671006119fef4c48b8112778fd1e0fce
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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