1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → [8-(4-Chloro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[1-(3-methyl-[1,2,4]thiadiazol-5-yl)-piperidin-4-yl]-amine

HRID 451462Notes

Reaction equation

HRID 451462 reaction equation
[CH3:1][C:2]1[N:6]=[C:5]([N:7]2[CH2:12][CH2:11][CH:10]([NH2:13])[CH2:9][CH2:8]2)[S:4][N:3]=1.Br[C:15]1[N:30]=[C:18]2[C:19]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)=[CH:20][CH:21]=[CH:22][N:17]2[N:16]=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+]>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.C(Cl)(Cl)Cl.[Pd].[Pd]>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([C:19]2[C:18]3[N:17]([N:16]=[C:15]([NH:13][CH:10]4[CH2:9][CH2:8][N:7]([C:5]5[S:4][N:3]=[C:2]([CH3:1])[N:6]=5)[CH2:12][CH2:11]4)[N:30]=3)[CH:22]=[CH:21][CH:20]=2)=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 4445035Phenolate SodiumHCID 583978761-(3-Methyl-1,2,4-thiadiazol-5-yl)piperidin-4-amineHCID 673434472-Bromo-8-(4-chlorophenyl)-[1,2,4]triazolo[1,5-a]pyridine

Product 1

HCID 53353913[8-(4-Chloro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[1-(3-methyl-[1,2,4]thiadiazol-5-yl)-piperidin-4-yl]-amine

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 312751,4-DioxaneSolvent

Procedure

Through a suspension of 1-(3-methyl-1,2,4-thiadiazol-5-yl)piperidin-4-amine (40 mg, 202 μmol), 2-bromo-8-(4-chlorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (74.7 mg, 242 μmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (9.34 mg, 16.1 μmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (8.35 mg, 8.07 μmol) and sodium phenoxide (35.1 mg, 303 μmol) in dry dioxane (3 mL) was bubbled argon for 5 minutes. The mixture was then irradiated at 150° C. for 60 minutes. The crude material was purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane). The title compound was obtained as an off-white foam (42 mg, 49%).

Workup

  1. customwas bubbled argon for 5 minutes
  2. customThe mixture was then irradiated at 150° C. for 60 minutes
  3. customThe crude material was purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane)

Sources & evidence

ORD record
ord-1e7ac74acf4e4d82bcb0f8b2bed4d28e
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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