Potassium Phosphate, Tribasic → 8-(Tert-butyldimethylsilyloxy)-2-(6-cyclopropyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinoline

HRID 876444Notes

Reaction equation

HRID 876444 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:20]=[CH:19][C:18]4[C:13](=[C:14]([O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH:15]=[CH:16][CH:17]=4)[N:12]=3)=[N:9][N:10]=2)[CH:7]=1.[CH:29]1(B(O)O)[CH2:31][CH2:30]1.P(C1CCCCC1)(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[Si:22]([O:21][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:13]=1[N:12]=[C:11]([C:8]1[N:6]3[CH:7]=[C:2]([CH:29]4[CH2:31][CH2:30]4)[CH:3]=[CH:4][C:5]3=[N:10][N:9]=1)[CH:20]=[CH:19]2)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 672305262-(6-Bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-8-(tert-butyldimethylsilyloxy)quinoline

Product 1

HCID 672305218-(Tert-butyldimethylsilyloxy)-2-(6-cyclopropyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolineYield 34.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

2-(6-Bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-8-(tert-butyldimethylsilyloxy)quinoline (0.500 g, 1.10 mmol), cyclopropylboronic acid (0.123 g, 1.43 mmol), Pd(OAc)2 (0.012 g, 0.0549 mmol), P(Cy)3 (0.031 g, 0.110 mmol), and K3PO4 (0.699 g, 3.29 mmol) were combined with 5.5 mL toluene and 0.55 mL H2O (both degassed with nitrogen 30 minutes prior to use). The mixture was sonicated and put on a 100° C. reaction block and stirred for 3 hours. The reaction mixture was cooled to ambient temperature, diluted with toluene, vacuum filtered through compressed Celite, rinsed with toluene, and the filtrate was concentrated. The crude material was purified on silica (5% to 60% ethyl acetate in dichloromethane) to give the title compound (0.159 g, 0.382 mmol, 34.8% yield) as a brown foam.

Workup

  1. customboth degassed with nitrogen 30 minutes
  2. customThe mixture was sonicated
  3. customput on a 100° C.
  4. customreaction block
  5. filtrationfiltered
  6. washrinsed with toluene
  7. concentrationthe filtrate was concentrated
  8. customThe crude material was purified on silica (5% to 60% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-23ee5b9c2efa4d36acbbc12742bb08a1
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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