4-Bromopyridinium chloride → 5-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine

HRID 1776392Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1776392
[CH3:1][O:2][C:3]1[C:4]([NH2:27])=[N:5][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[N:10]=2)=[N:7][CH:8]=1.Cl.Br[C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1.CC([O-])(C)C.[Na+]>CN(C=O)C.ClCCl.C1(/C=C/C(=O)/C=C/C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:1][O:2][C:3]1[C:4]([NH:27][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)=[N:5][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[N:10]=2)=[N:7][CH:8]=1

Komponenten

7

Edukt 3

HCID 881004-Bromopyridinium chloride2×HCID 23676156Sodium t-butoxide2×HCID 867324165-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]pyrimidin-4-amine

Produkt 1

HCID 867324175-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 15673654(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one palladiumKatalysator2×HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

205 mg of 5-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]pyrimidin-4-amine (1-4-1, 0.568 mmol, 1 eq.), 121.6 mg of 4-bromopyridine hydrochloride (1:1) (0.625 mmol. 1.1 eq.), 136.5 mg of sodium 2-methylpropan-2-olate (1.42 mmol, 2.5 eq.), 106.2 mg of 1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (0.171 mmol, 0.3 eq.) and 52.0 mg of (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) (0.057 mmol, 0.1 eq.) were suspended in 3 ml of dry DMF under nitrogen atmosphere. The reaction mixture was stirred for two days at 100° C. 122 mg of 4-bromopyridine hydrochloride (1:1) (0.625 mmol. 1.1 eq.), 137 mg of sodium 2-methylpropan-2-olate (1.42 mmol, 2.5 eq.), 106 mg of 1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (0.171 mmol, 0.3 eq.) and 52.0 mg of (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) (0.057 mmol, 0.1 eq.) were added and stirred for further 24 hours. The mixture was cooled down to room temperature, diluted with 10 ml dichloromethane and filtered off. The filtrate was concentrated in vacuo. The residue was purified by flash chromatography to yield 126 mg (0.23 mmol, 81%) of the analytically pure target compound.

Aufarbeitung

  1. stirringstirred for further 24 hours
  2. temperatureThe mixture was cooled down to room temperature
  3. filtrationfiltered off
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by flash chromatography
  6. customto yield 126 mg (0.23 mmol, 81%) of the analytically pure target compound

Quellen und Nachweise

ORD-Eintrag
ord-090713e78eb3411ab218e958c45e3687
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09265763B2

Notizen zur Reaktion

Wird geladen…