Sodium Carbonate → tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate

HRID 1529350Notes

Reaction equation

HRID 1529350 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[F:18])[CH:9]=2)[N:4]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[C:35]([N:39]3[CH2:44][CH2:43][CH:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:41][CH2:40]3)[CH:36]=[N:37][CH:38]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([F:17])[C:11]=1[C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:3]=[C:2]2[C:33]1[CH:34]=[C:35]([N:39]2[CH2:40][CH2:41][CH:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])[CH2:43][CH2:44]2)[CH:36]=[N:37][CH:38]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 679597623-bromo-5-(2,6-difluoro-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-indazoleHCID 67959870Tert-butyl 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidin-4-ylcarbamate

Product 1

HCID 67960050tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-ylcarbamateYield 89%

Reagents, catalysts & solvents 2

HCID 178478230HCID 178478230, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 3-bromo-5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (90 mg, 0.229 mmol), tert-butyl 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidin-4-ylcarbamate (115 mg, 0.286 mmol), Na2CO3, 2.0 M (0.229 mL, 0.458 mmol) and dichloro 1,1′-bis(diphenylphosphino) ferrocene palladium (II) (18.69 mg, 0.023 mmol, Strem) in dioxane (3 mL) was capped, degassed and backfilled with argon. The reaction was heated to 135° C. in a microwave for 45 min. The reaction mixture was diluted with EtOAc (50 mL) and washed with brine (50 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluent: 0-3% MeOH/DCM), affording tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (120 mg, 89%). MS (ESI, pos. ion) m/z: 590.3 (M+1).

Workup

  1. customwas capped
  2. customdegassed
  3. additionThe reaction mixture was diluted with EtOAc (50 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography (eluent: 0-3% MeOH/DCM)

Sources & evidence

ORD record
ord-206cca678a2d45ff80490bbf37155eee
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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