Tri-o-tolylphosphine → 3-(4-(4-Benzyloxy-benzyl)-pyrazol-1-yl)-pyridin-2-ylamine

HRID 1690987

Reaktionsgleichung

Reaktionsgleichung von HRID 1690987
Br[C:2]1[CH:3]=[N:4][N:5]([C:7]2[C:8]([NH2:13])=[N:9][CH:10]=[CH:11][CH:12]=2)[CH:6]=1.[CH2:14]([O:21][C:22]1[CH:41]=[CH:40][C:25]([CH2:26][Sn](CCCC)(CCCC)CCCC)=[CH:24][CH:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN1CCCC1=O>[CH2:14]([O:21][C:22]1[CH:23]=[CH:24][C:25]([CH2:26][C:2]2[CH:3]=[N:4][N:5]([C:7]3[C:8]([NH2:13])=[N:9][CH:10]=[CH:11][CH:12]=3)[CH:6]=2)=[CH:40][CH:41]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Komponenten

6

Edukt 3

HCID 80271Tri-o-tolylphosphineHCID 592550903-(4-Bromo-pyrazol-1-yl)-pyridin-2-ylamineHCID 59255482(4-Benzyloxy-benzyl)-tributyl-stannane

Produkt 1

HCID 592554413-(4-(4-Benzyloxy-benzyl)-pyrazol-1-yl)-pyridin-2-ylamineAusbeute 5,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a mixture of 3-(4-bromo-pyrazol-1-yl)-pyridin-2-ylamine (34 mg, 0.14 mmol) described in Manufacturing Example 39-1-4, (4-benzyloxy-benzyl)-tributyl-stannane (84 mg, 0.17 mmol) described in Manufacturing Example 39-2-1 and N-methylpyrrolidinone (1.5 mL) were added tri-o-tolylphosphine (17 mg, 0.057 mmol) and palladium (II) acetate (3.2 mg, 0.014 mmol) at room temperature, which was stirred for 5 hours at 120° C. The reaction mixture was cooled to room temperature, and filtered after addition of an aqueous potassium fluoride solution and ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) to obtain the title compound (2.6 mg, 4%) as a trifluoroacetic acid salt.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. additionafter addition of an aqueous potassium fluoride solution and ethyl acetate
  4. customThe organic layer was separated
  5. washwashed with saturated aqueous sodium chloride
  6. customthe solvent was evaporated under a reduced pressure
  7. customThe residue was purified by reverse-phase high performance liquid chromatography (
  8. additioncontaining 0.1% trifluoroacetic acid)

Quellen und Nachweise

ORD-Eintrag
ord-338a096222ce480ca310f183ecb059c8
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08153662B2

Verknüpfte Notizen

Wird geladen…