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Potassium Carbonate → N-(6-((R)-1-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)ethoxy)-2-(4-fluorobenzyl-thio)pyrimidin-4-yl)-3-methylazetidine-1-sulfonamide

HRID 1506839
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1506839
Cl[C:2]1[CH:7]=[C:6]([O:8][C@@H:9]([C@@H:11]2[CH2:15][O:14][C:13]([CH3:17])([CH3:16])[O:12]2)[CH3:10])[N:5]=[C:4]([S:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[N:3]=1.[CH3:27][CH:28]1[CH2:31][N:30]([S:32]([NH2:35])(=[O:34])=[O:33])[CH2:29]1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O1CCOCC1.O.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]>[CH3:16][C:13]1([CH3:17])[O:12][C@H:11]([C@H:9]([O:8][C:6]2[N:5]=[C:4]([S:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:3]=[C:2]([NH:35][S:32]([N:30]3[CH2:31][CH:28]([CH3:27])[CH2:29]3)(=[O:34])=[O:33])[CH:7]=2)[CH3:10])[CH2:15][O:14]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 714875803-Methylazetidine-1-sulfonamide2×HCID 866766774-Chloro-6-((R)-1-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethoxy)-2-(4-fluorobenzylthio)pyrimidine

Produkt 1

HCID 71231083
N-(6-((R)-1-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)ethoxy)-2-(4-fluorobenzyl-thio)pyrimidin-4-yl)-3-methylazetidine-1-sulfonamide
Ausbeute 81,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of the sub-title product of step (iii) (94 g) dissolved in dioxane (700 mL) was treated with 3-methylazetidine-1-sulfonamide (Intermediate B) (42.5 g), potassium carbonate (65.1 g), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (11.2 g) and tris(dibenzylideneacetone)dipalladium(0) (10.8 g) under nitrogen. The resulting mixture was stirred at 100° C. for 60 minutes. The reaction mixture was diluted with water (500 mL) and extracted with ethyl acetate (500 mL). The organics were dried over magnesium sulfate, filtered and evaporated in vacuo to afford crude product. The crude product was purified by flash silica chromatography with elution 30% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford the sub-title product (98 g) as a red oil.

Aufarbeitung

  1. extractionextracted with ethyl acetate (500 mL)
  2. dry with materialThe organics were dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography with elution 30% ethyl acetate in isohexane
  7. customPure fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-4d8ea007624a4aa18e18330edd5a60db
Quelldatensatz
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09221782B2

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