Water → HCID 89442647, Verbindung

HRID 632725Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 632725
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[C:19]([Cl:21])[C:18]([Cl:22])=[CH:17][C:16]=3[OH:23])[CH2:10][CH2:9]2)[C:3]=1[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1.C(OC([N:38]1[CH2:41][CH:40](I)[CH2:39]1)=O)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[NH:38]1[CH2:41][CH:40]([O:23][C:16]2[CH:17]=[C:18]([Cl:22])[C:19]([Cl:21])=[CH:20][C:15]=2[CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH2:9][CH2:10]2)[CH2:39]1

Komponenten

6

Edukt 4

HCID 962WaterHCID 10796Cesium carbonateHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 89442445HCID 89442445, Verbindung

Produkt 1

HCID 89442647HCID 89442647, VerbindungAusbeute 40,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A reaction mixture of 2-{4-[6-amino-5-(4-fluoro-phenyl)-pyrimidin-4-yl]-piperazin-1-ylmethyl}-4,5-dichloro-phenol (80.0 mg; 0.18 mmol; 1.00 eq.), 3-iodo-azetidine-1-carboxylic acid tert-butyl ester (60.6 mg; 0.21 mmol; 1.20 eq.) and cesium carbonate (116.2 mg; 0.36 mmol; 2.00 eq.) in DMF (1 ml) was stirred at 90° C. overnight. The reaction solution was poured to water and extracted with ethyl acetate, The separated organic layer was washed with brine, dried and concentrated, which was then dissolved in methanol (1 ml) followed by adding 4.0 M HCl in dioxane (2 ml) and stirred at RT overnight. The reaction mixture was concentrated and purified by Waters prep-HPLC (acidic condition) to yield the title compounds (37 mg, yield 33.6%). LC-MS: (M+1=504, obsd.=504/506).

Aufarbeitung

  1. extractionextracted with ethyl acetate
  2. washThe separated organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated
  5. dissolutionwhich was then dissolved in methanol (1 ml)
  6. additionby adding 4.0 M HCl in dioxane (2 ml)
  7. stirringstirred at RT overnight
  8. concentrationThe reaction mixture was concentrated
  9. custompurified by Waters prep-HPLC (acidic condition)

Quellen und Nachweise

ORD-Eintrag
ord-291fb5e366ba4ebab0cba7a5a334f975
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321760B2

Notizen zur Reaktion

Wird geladen…