Toluene → tert-butyl methyl(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)carbamate

HRID 2389247Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2389247
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:14][CH2:13]2)=[N:4][N:3]=1.[CH3:27][N:28]1[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=[N:29]1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.C(O)C>[CH3:26][N:18]([CH:15]1[CH2:16][CH2:17][N:12]([C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:2]([C:32]3[N:28]([CH3:27])[N:29]=[CH:30][CH:31]=3)=[N:3][N:4]=2)[CH2:13][CH2:14]1)[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22]

Komponenten

8

Edukt 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 59627406tert-Butyl 1-(4-bromophthalazin-1-yl)piperidin-4-yl(methyl)carbamate

Produkt 1

HCID 59627389tert-butyl methyl(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)carbamateAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Charge a reaction tube with tert-butyl 1-(4-bromophthalazin-1-yl)piperidin-4-yl(methyl)carbamate (500 mg, 1 2 mmol), 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (370 mg, 1.8 mmol), sodium carbonate (252 mg, 2.4 mmol), toluene (3.75 mL), ethanol (1.25 mL), and water (1.25 mL). Degas the reaction mixture with nitrogen for 10 min. Add tetrakis (triphenylphosphine) palladium (137.1 mg, 118.7 μmol). Bubble nitrogen through the reaction mixture for another 10 min. Cap the reaction vial and heat at 90° C. overnight. Cool the reaction and filter through a silica gel pad eluting with 5% MeOH:CH2Cl2. Concentrate the fractions under reduced pressure. Purify the resulting residue using silica gel chromatography (2% 2 N NH3 in MeOH:CH2Cl2) to obtain the final product (345.6 mg, 69%). ES/MS m/z 423.2 (M+1).

Aufarbeitung

  1. customDegas the reaction mixture with nitrogen for 10 min
  2. customCap
  3. customthe reaction vial
  4. temperatureCool
  5. customthe reaction
  6. filtrationfilter through a silica gel pad
  7. washeluting with 5% MeOH
  8. concentrationConcentrate the fractions under reduced pressure
  9. customPurify the resulting residue

Quellen und Nachweise

ORD-Eintrag
ord-1a8975bb462e4b2baa4157fa77c9afc7
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08273742B2

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