Potassium Carbonate → (4-(1-((R)-1-(4-chloro-2-(trifluoromethyl)phenyl)ethyl)-1H-benzo[d][1,2,3]triazol-6-yl)-5,6-dihydropyridin-1(2H)-yl)((R)-piperidin-2-yl)methanone

HRID 1747185Notes

Reaction equation

HRID 1747185 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[N:8][N:7]([C@@H:10]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[C:19]([F:22])([F:21])[F:20])[CH3:11])[C:6]=2[CH:23]=1.C(O[C:29]([N:31]1[CH2:36][CH:35]=[C:34](B(O)O)[CH2:33][CH2:32]1)=[O:30])(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>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.C1(C)C=CC=CC=1.C(O)C>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([C@H:10]([N:7]2[C:6]3[CH:23]=[C:2]([C:34]4[CH2:33][CH2:32][N:31]([C:29]([C@H:32]5[CH2:33][CH2:34][CH2:35][CH2:36][NH:31]5)=[O:30])[CH2:36][CH:35]=4)[CH:3]=[CH:4][C:5]=3[N:9]=[N:8]2)[CH3:11])=[C:13]([C:19]([F:22])([F:21])[F:20])[CH:14]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 21931462(1-(tert-Butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acidHCID 86688458(R)-6-bromo-1-(1-(4-chloro-2-(trifluoromethyl)phenyl)ethyl)-1H-benzo[d][1,2,3]triazole

Product 1

HCID 86688457(4-(1-((R)-1-(4-chloro-2-(trifluoromethyl)phenyl)ethyl)-1H-benzo[d][1,2,3]triazol-6-yl)-5,6-dihydropyridin-1(2H)-yl)((R)-piperidin-2-yl)methanoneYield 162.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (R)-6-bromo-1-(1-(4-chloro-2-(trifluoromethyl)phenyl)ethyl)-1H-benzo[d][1,2,3]triazole (0.32 g, 0.8 mmol), (N-t-butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)boronic acid pincol ester (0.27 g, 0.8 mmol), Pd(PPh3)4 (0.046 g, 0.039 mmol), and 2 M aqueous potassium carbonate (1.2 mL, 2.4 mmol) in 2:1 toluene/ethanol (3.6 mL) was purged with nitrogen for 5 min, and then heated at 100° C. for 2 h. After cooling to room temperature, the mixture was extracted with ethyl acetate (15 mL). The organic layer was washed with brine, dried (Na2SO4), and concentrated in vacuo. The resulting crude material was purified by flash chromatography (SiO2, 0-100% ethyl acetate in hexanes) to afford the desired product (0.33 g, 0.65 mmol, 83%).

Workup

  1. customwas purged with nitrogen for 5 min
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture was extracted with ethyl acetate (15 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude material was purified by flash chromatography (SiO2, 0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3ff0839997f64a9c95b4bb304579e24d
Source dataset
uspto-grants-2015_10
Patent number
US09150550B2

Reaction notes

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