Benzyl Alcohol → 8-benzyloxy-4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

HRID 1773922

Reaktionsgleichung

Reaktionsgleichung von HRID 1773922
Br[C:2]1[C:15]2[CH2:14][CH2:13][N:12]3[C:8](=[N:9][C:10]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:11]3)[CH:7]([O:22][CH:23]3[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH2:30]([OH:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.CN1CCC(OC2C3C=CC=CC=3CCN3C2=NC(C2C=CC=CC=2)=C3)CC1.CC1C=NC2C(C=1C)=CC=C1C=2N=CC(C)=C1C.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Cu]I>[CH2:30]([O:37][C:2]1[C:15]2[CH2:14][CH2:13][N:12]3[C:8](=[N:9][C:10]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:11]3)[CH:7]([O:22][CH:23]3[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Komponenten

8

Edukt 5

HCID 244Benzyl AlcoholHCID 10796Cesium carbonateHCID 742653,4,7,8-Tetramethyl-1,10-phenanthrolineHCID 726957794-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azuleneHCID 867040028-bromo-4-(1-methyl-piperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

Produkt 1

HCID 867040078-benzyloxy-4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of 8-bromo-4-(1-methyl-piperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 231) (276 mg, 0, 40 mmole) in anhydrous toluene (5 mL) in a screw-capped vial are added benzyl alcohol (87 mg, 0, 80 mmole), copper(I) iodide (15.3 mg, 0.080 mmole), ground 4A molecular sieves (133 mg), 3,4,7,8-tetramethyl-1,10-phenanthroline (38 mg, 0, 16 mmole) and cesium carbonate (261 mg, 0, 80 mmole). The vial is evacuated and filled with argon. The reaction mixture is stirred at 90° C. for 3 days. Water and ammonia are added to the reaction mixture, and the aqueous phase is extracted three times with dichloromethane. Pooled organic extracts are dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1°)/0 formic acid (B), focus gradient from 23% (B) to 33% (B) in 10 minutes) to afford 8-benzyloxy-4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene melting at 68° C.

Aufarbeitung

  1. customThe vial is evacuated
  2. additionfilled with argon
  3. additionWater and ammonia are added to the reaction mixture
  4. extractionthe aqueous phase is extracted three times with dichloromethane
  5. dry with materialPooled organic extracts are dried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent is removed under reduced pressure
  8. customThe residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1°)/0 formic acid (B)
  9. customin 10 minutes

Quellen und Nachweise

ORD-Eintrag
ord-1a6c11104e2b47c79cf9c052b26be281
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09255101B2

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