1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → N-(1-(2-Chloropyridin-4-yl)piperidin-4-yl)-8-(3,4-difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 451499Notes

Reaction equation

HRID 451499 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:9]=[C:8]([N:10]2[CH2:15][CH2:14][CH:13]([NH2:16])[CH2:12][CH2:11]2)[CH:7]=[CH:6][N:5]=1.Br[C:18]1[N:34]=[C:21]2[C:22]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[CH:27]=3)=[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>[Cl:3][C:4]1[CH:9]=[C:8]([N:10]2[CH2:15][CH2:14][CH:13]([NH:16][C:18]3[N:34]=[C:21]4[C:22]([C:26]5[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[CH:27]=5)=[CH:23][CH:24]=[CH:25][N:20]4[N:19]=3)[CH2:12][CH2:11]2)[CH:7]=[CH:6][N:5]=1

Participants

6

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 4445035Phenolate SodiumHCID 673424362-Bromo-8-(3,4-difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridineHCID 866567091-(2-Chloropyridin-4-yl)piperidin-4-amine dihydrochloride

Product 1

HCID 58398048N-(1-(2-Chloropyridin-4-yl)piperidin-4-yl)-8-(3,4-difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 1-(2-chloropyridin-4-yl)piperidin-4-amine dihydrochloride (142 mg, 0.50 mmol) in dichloromethane was washed with 2 N NaOH, the aqueous layer extracted with dichloromethane, the combined organic layers dried over sodium sulfate and evaporated. The “free-base” residue was dissolved in dioxane (4 mL), 2-bromo-8-(3,4-difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (prepared in analogy to example 66a-d) (170 mg, 0.55 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (23 mg, 8 mol %), tris(dibenzylideneacetone)dipalladium chloroform complex (21 mg, 4 mol %) and sodium phenoxide (87 mg, 0.75 mmol) were added, Ar was bubbled through the reaction mixture for 5 minutes and then irradiated at 130° C. in the microwave for 1 hour. The crude material was purified by flash chromatography (silica-NH2, 20 g, 0 to 100% ethyl acetate in heptane). The title compound was obtained as a yellow solid (103 mg, 47%).

Workup

  1. washwas washed with 2 N NaOH
  2. extractionthe aqueous layer extracted with dichloromethane
  3. dry with materialthe combined organic layers dried over sodium sulfate
  4. customevaporated
  5. dissolutionThe “free-base” residue was dissolved in dioxane (4 mL)
  6. customAr was bubbled through the reaction mixture for 5 minutes
  7. customirradiated at 130° C. in the microwave for 1 hour
  8. customThe crude material was purified by flash chromatography (silica-NH2, 20 g, 0 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-6c71c94ed4aa41ad8caf2c26287dd9c0
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

Loading…