Sodium Carbonate → 4-{4-[6-(6-Trifluoromethyl-pyridin-3-ylamino)-pyridin-3-yl]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 76048Notes

Reaction equation

HRID 76048 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17](B3OC(C)(C)C(C)(C)O3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:30]1[CH:31]=[CH:32][C:33]([NH:36][C:37]2[CH:38]=[N:39][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:41][CH:42]=2)=[N:34][CH:35]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([C:30]3[CH:35]=[N:34][C:33]([NH:36][C:37]4[CH:38]=[N:39][C:40]([C:43]([F:45])([F:46])[F:44])=[CH:41][CH:42]=4)=[CH:32][CH:31]=3)=[CH:16][CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 53629760tert-Butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine-1-carboxylateHCID 66615754(5-Bromo-pyridin-2-yl)-(6-trifluoromethyl-pyridin-3-yl)-amine

Product 1

HCID 666159164-{4-[6-(6-Trifluoromethyl-pyridin-3-ylamino)-pyridin-3-yl]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

4-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-piperidine-1 carboxylic acid tert-butyl ester (1.56 g, 4.1 mmol) and (5-Bromo-pyridin-2-yl)-(6-trifluoromethyl-pyridin-3-yl)-amine (1.28 g, 4.0 mmol) were dissolved in DME (8 mL) in a pressure vessel, and to the solution was added PdCl2dppf (100 mg, 0.12 mmol) and Na2CO3 (2.0M, 4.0 mL, 8.1 mmol). The mixture was sparged with nitrogen for 10 minutes, then the vessel was sealed and stirred at 80° C. for 18 hours. The mixture was partitioned between EtOAc and saturated aqueous NH4Cl, washed with brine, dried with magnesium sulfate, filtered, and concentrated via rotary evaporation. The crude material was purified via column chromatography on silica gel, eluting with a gradient of EtOAc/hexanes (10-50%) to obtain the target compound as a solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (br. s., 2H) 1.42 (s, 9H) 1.52 (qd, J=12.63, 4.55 Hz, 2H) 1.77 (m, 2H) 2.66-2.76 (m, 1H) 4.09 (m, 2H) 7.03 (d, J=8.59 Hz, 1H) 7.34 (d, J=8.34 Hz, 2H) 7.60 (d, J=8.08 Hz, 2H) 7.79 (d, J=8.84 Hz, 1H) 7.99 (dd, J=8.72, 2.65 Hz, 1H) 8.56 (d, J=2.53 Hz, 1H) 8.91 (d, J=2.53 Hz, 1H) 9.87 (s, 1H); MS (M+H)+499.3.

Workup

  1. customThe mixture was sparged with nitrogen for 10 minutes
  2. customthe vessel was sealed
  3. customThe mixture was partitioned between EtOAc and saturated aqueous NH4Cl
  4. washwashed with brine
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated via rotary evaporation
  8. customThe crude material was purified via column chromatography on silica gel
  9. washeluting with a gradient of EtOAc/hexanes (10-50%)

Sources & evidence

ORD record
ord-123d9f0f95a6444d9e601ce849e30fc3
Source dataset
uspto-grants-2014_09
Patent number
US08835451B2

Reaction notes

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