Chloroform → 2-{8-(4-Chloro-phenyl)-2-[1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamino]-[1,2,4]triazolo[1,5-a]pyridin-5-yl}-propan-2-ol

HRID 451453Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 451453
Br[C:2]1[N:21]=[C:5]2[C:6]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)=[CH:7][CH:8]=[C:9]([C:10]([OH:13])([CH3:12])[CH3:11])[N:4]2[N:3]=1.[CH3:22][C:23]1[N:28]=[CH:27][N:26]=[C:25]([N:29]2[CH2:34][CH2:33][CH:32]([NH2:35])[CH2:31][CH2:30]2)[CH:24]=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]>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([C:6]2[C:5]3[N:4]([N:3]=[C:2]([NH:35][CH:32]4[CH2:33][CH2:34][N:29]([C:25]5[CH:24]=[C:23]([CH3:22])[N:28]=[CH:27][N:26]=5)[CH2:30][CH2:31]4)[N:21]=3)[C:9]([C:10]([OH:13])([CH3:12])[CH3:11])=[CH:8][CH:7]=2)=[CH:15][CH:16]=1

Komponenten

8

Edukt 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 673355472-[2-Bromo-8-(4-chloro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]-propan-2-ol

Produkt 1

HCID 533536302-{8-(4-Chloro-phenyl)-2-[1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamino]-[1,2,4]triazolo[1,5-a]pyridin-5-yl}-propan-2-ol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

A solution of 2-[2-bromo-8-(4-chloro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]-propan-2-ol (42 mg, 0.11 mmol), 1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamine (18 mg, 0.1 mmol) and sodium phenoxide (17 mg, 0.15 mmol) in dry 1,4-dioxane (6 mL) in a sealed tube was purged with argon for 10 minutes. Pd2(dba)3.CHCl3 (8 mg, 0.012 mmol) and xanthphos (2 mg) were added to the solution and degassing continued for another 5 minutes before the reaction mixture was heated to 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 white solid (7 mg, 13%). MS ESI (m/e): 478.0 [(M+H)+].

Aufarbeitung

  1. customdegassing
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionwater (10 mL) was added
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. dry with materialthe combined organic phases were dried over sodium sulfate
  6. customthe solvent was evaporated
  7. customthe residue purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-7b7f758ae6b9401cb927e1bea9f30f4e
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08486967B2

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