Sodium Carbonate → 4-(1H-indazol-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 68747

Reaction equation

HRID 68747 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C([O-])([O-])=O.[K+].[K+].C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[C:11]([O:15][C:16]([N:18]1[CH2:19][CH:20]=[C:21]([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[N:7][NH:8]3)=[CH:4][CH:3]=2)[CH2:22][CH2:23]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 178424716-Bromo-1H-indazole

Product 1

HCID 674494164-(1H-indazol-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 6-bromoindazole (2.0 g, 10.2 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (3.5 g, 11.2 mmol) and Pd(PPh3)4 (1.2 g, 1.0 mmol) under N2 were added 1,4-dioxane (80 mL), followed by addition of K2CO3 (2 M in H2O, 20 mL, 40 mmol). The resulting mixture was heated at 110° C. for 16 h, then cooled to room temperature. The resulting mixture was then treated with saturated Na2CO3 aqueous solution. The resulting mixture was extracted with EtOAc (3×). The combined extracts were washed with brine and then dried over Na2SO4. The resulting mixture was filtered, concentrated under reduced pressure, and the residue purified by flash chromatography on silica-gel (gradient eluent heptane to 60% EtOAc in heptane) to yield 4-(1H-indazol-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as brownish foam solid.

Workup

  1. temperaturecooled to room temperature
  2. extractionThe resulting mixture was extracted with EtOAc (3×)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationThe resulting mixture was filtered
  6. concentrationconcentrated under reduced pressure
  7. customthe residue purified by flash chromatography on silica-gel (gradient eluent heptane to 60% EtOAc in heptane)

Sources & evidence

ORD record
ord-4a50c4d2f95c495ca72eca4eeaccd606
Source dataset
uspto-grants-2014_09
Patent number
US08822447B2

Linked notes

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