1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 8-(2-Chloro-4-fluorophenyl)-N-(1-(6-methylpyrimidin-4-yl)piperidin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 451455Notes

Reaction equation

HRID 451455 reaction equation
Cl.Cl.[CH3:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([N:10]2[CH2:15][CH2:14][CH:13]([NH2:16])[CH2:12][CH2:11]2)[CH:5]=1.Br[C:18]1[N:34]=[C:21]2[C:22]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=3[Cl:33])=[CH:23][CH:24]=[CH:25][N:20]2[N:19]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[O-]C1C=CC=CC=1.[Na+]>ClCCl.O1CCOCC1>[Cl:33][C:27]1[CH:28]=[C:29]([F:32])[CH:30]=[CH:31][C:26]=1[C:22]1[C:21]2[N:20]([N:19]=[C:18]([NH:16][CH:13]3[CH2:14][CH2:15][N:10]([C:6]4[CH:5]=[C:4]([CH3:3])[N:9]=[CH:8][N:7]=4)[CH2:11][CH2:12]3)[N:34]=2)[CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 4445035Phenolate SodiumHCID 673364492-Bromo-8-(2-chloro-4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridineHCID 673421331-(6-Methylpyrimidin-4-yl)piperidin-4-amine dihydrochloride

Product 1

HCID 533537188-(2-Chloro-4-fluorophenyl)-N-(1-(6-methylpyrimidin-4-yl)piperidin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amineYield 44.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

1-(6-Methylpyrimidin-4-yl)piperidin-4-amine dihydrochloride (133 mg, 0.5 mmol) was suspended in dichloromethane (15 mL) and then extracted with aqueous sodium hydroxide (2 M, 10 mL). The aqueous layer was extracted with dichloromethane (15 mL) and the organic layers were combined, dried over sodium sulfate and evaporated carefully. After addition of 2-bromo-8-(2-chloro-4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (180 mg, 0.55 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (23.1 mg, 0.04 mmol), tris(dibenzylideneacetone)dipalladium(o) chloroform adduct (21 mg, 0.02 mmol) and sodium phenoxide (87 mg, 0.75 mmol) in dry 1,4-dioxane (4 mL) the reaction mixture was stirred under an argon atmosphere for 60 minutes at 130° C. in the microwave. Concentration and purification of the residue by chromatography (SiO2, heptane:ethyl acetate 3:1 to 0:1) afforded the title compound as yellow foam (97 mg, 44%).

Workup

  1. extractionextracted with aqueous sodium hydroxide (2 M, 10 mL)
  2. extractionThe aqueous layer was extracted with dichloromethane (15 mL)
  3. dry with materialdried over sodium sulfate
  4. customevaporated carefully
  5. concentrationConcentration and purification of the residue by chromatography (SiO2, heptane:ethyl acetate 3:1 to 0:1)

Sources & evidence

ORD record
ord-dad9f949b52d456f8bc8466615647673
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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