1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 3,3-Difluoro-4-[8-(2,3,4-trifluoro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 451561Notes

Reaction equation

HRID 451561 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[C:10]([F:16])([F:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:18]1[N:35]=[C:21]2[C:22]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[C:27]=3[F:34])=[CH:23][CH:24]=[CH:25][N:20]2[N:19]=1.[O-]C1C=CC=CC=1.[Na+].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>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]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:18]2[N:35]=[C:21]3[C:22]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[C:27]=4[F:34])=[CH:23][CH:24]=[CH:25][N:20]3[N:19]=2)[C:10]([F:16])([F:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 4445035Phenolate SodiumHCID 56932105tert-Butyl 4-amino-3,3-difluoropiperidine-1-carboxylateHCID 67342605HCID 67342605, compound

Product 1

HCID 673428633,3-Difluoro-4-[8-(2,3,4-trifluoro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

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

Conditions

Temperature
160 °C

Procedure

Through a suspension of 4-amino-3,3-difluoro-piperidine-1-carboxylic acid tert-butyl ester (90 mg, 381 μmol), 2-bromo-8-(2,3,4-trifluorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (prepared in analogy to example 66a-d, 162 mg, 495 μmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (15.8 mg, 15.2 μmol), sodium phenoxide (65.2 mg, 533 μmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (17.6 mg, 30.5 μmol) in dry dioxane (5.0 mL) was bubbled argon for 5 minutes, then heated to 160° C. in the microwave for 60 minutes. The catalyst was filtered off, washed with CH2Cl2 and the solvents evaporated. The residue was purified by flash chromatography (silica gel, 70 g, 0% to 100% EtOAc in heptane). The title compound was obtained as orange solid (27 mg, 15%).

Workup

  1. customwas bubbled argon for 5 minutes
  2. filtrationThe catalyst was filtered off
  3. washwashed with CH2Cl2
  4. customthe solvents evaporated
  5. customThe residue was purified by flash chromatography (silica gel, 70 g, 0% to 100% EtOAc in heptane)

Sources & evidence

ORD record
ord-f989cf8297714e67a8f2f76e7f45a5f3
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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