Chloroform → [8-(4-Chloro-phenyl)-6-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[1-(6-methyl-pyrimidin-4-yl)-piperidin-4-yl]-amine

HRID 451447Notes

Reaction equation

HRID 451447 reaction equation
Br[C:2]1[N:20]=[C:5]2[C:6]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)=[CH:7][C:8]([CH:10]3[CH2:12][CH2:11]3)=[CH:9][N:4]2[N:3]=1.[CH3:21][C:22]1[N:27]=[CH:26][N:25]=[C:24]([N:28]2[CH2:33][CH2:32][CH:31]([NH2:34])[CH2:30][CH2:29]2)[CH:23]=1.[O-]C1C=CC=CC=1.[Na+].C(Cl)(Cl)Cl.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([C:6]2[C:5]3[N:4]([N:3]=[C:2]([NH:34][CH:31]4[CH2:32][CH2:33][N:28]([C:24]5[CH:23]=[C:22]([CH3:21])[N:27]=[CH:26][N:25]=5)[CH2:29][CH2:30]4)[N:20]=3)[CH:9]=[C:8]([CH:10]3[CH2:12][CH2:11]3)[CH:7]=2)=[CH:14][CH:15]=1

Participants

9

Reactant 5

HCID 6212ChloroformHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 4445035Phenolate SodiumHCID 166433141-(6-Methylpyrimidin-4-yl)piperidin-4-amineHCID 673344922-Bromo-8-(4-chloro-phenyl)-6-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridine

Product 1

HCID 53353629[8-(4-Chloro-phenyl)-6-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[1-(6-methyl-pyrimidin-4-yl)-piperidin-4-yl]-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

A solution of 2-bromo-8-(4-chloro-phenyl)-6-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridine (50 mg, 0.14 mmol), 1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamine (see example 94a, 23 mg, 0.12 mmol) and sodium phenoxide (21 mg, 0.2 mmol) in dry 1,4-dioxane (3 mL) in a sealed tube was purged with argon for 10 minutes. Pd2(dba)3.CHCl3 (8 mg, 0.01 mmol) and xanthphos (2 mg) were added to the solution and stirred at 160° C. for 15 hours. The reaction mixture was cooled to room temperature and water (10 mL) was added. The aqueous phase was extracted with ethyl acetate, the combined organic phases were dried over sodium sulfate, the solvent was evaporated and the residue purified by silica gel chromatography using dichloromethane/methanol as eluent. The title compound was obtained as a light brown solid (5 mg, 8%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe aqueous phase was extracted with ethyl acetate
  3. dry with materialthe combined organic phases were dried over sodium sulfate
  4. customthe solvent was evaporated
  5. customthe residue purified by silica gel chromatography

Sources & evidence

ORD record
ord-271db36bc1954f2ebae2731e7230495e
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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