Hydrochloric Acid → 4-[4-(4-Methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid 2-fluoro-1-fluoromethyl-ethyl ester

HRID 1931714Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1931714
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[F:13][CH2:14][CH:15]([OH:18])[CH2:16][F:17].N1C=CC=CC=1.Cl.FC(F)(F)C(O)=O.[CH3:33][S:34]([C:37]1[CH:58]=[CH:57][C:40]([O:41][C:42]2[N:47]=[CH:46][N:45]=[C:44]3[N:48]([CH:51]4[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]4)[N:49]=[CH:50][C:43]=23)=[CH:39][CH:38]=1)(=[O:36])=[O:35].C(N(C(C)C)CC)(C)C>ClCCCl.O>[F:13][CH2:14][CH:15]([O:18][C:2]([N:54]1[CH2:53][CH2:52][CH:51]([N:48]2[C:44]3=[N:45][CH:46]=[N:47][C:42]([O:41][C:40]4[CH:39]=[CH:38][C:37]([S:34]([CH3:33])(=[O:36])=[O:35])=[CH:58][CH:57]=4)=[C:43]3[CH:50]=[N:49]2)[CH2:56][CH2:55]1)=[O:4])[CH2:16][F:17]

Komponenten

9

Edukt 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 679851,3-Difluoro-2-propanolHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 669153264-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Produkt 1

HCID 579650444-[4-(4-Methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid 2-fluoro-1-fluoromethyl-ethyl esterAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

Triphosgene (208 mg, 0.7 mmol) was added to a solution of 1,3-difluoro-2-propanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 192 mg, 2 mmol) in a mixture of pyridine (2.2 mmol) and 1,2-dichloroethane (10 mL). The solution was stirred at 40° C. for 3 h and then cooled to room temperature. 1 M aqueous hydrochloric acid (2.5 mL) and water (5 mL) were added. The aqueous layer was extracted with dichloromethane and the combined organic layers were dried (magnesium sulfate), filtered, and evaporated. 4-(4-Methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 200 mg, 0.41 mmol) and diisopropylethylamine (350 μL) were added and the mixture was stirred for 15 min and then chromatographed, eluting with 50-75% ethyl acetate/hexanes, to give 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid 2-fluoro-1-fluoromethyl-ethyl ester (64 mg, 32%) as a foamy solid.

Aufarbeitung

  1. temperaturecooled to room temperature
  2. extractionThe aqueous layer was extracted with dichloromethane
  3. dry with materialthe combined organic layers were dried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. stirringthe mixture was stirred for 15 min
  7. customchromatographed
  8. washeluting with 50-75% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-ea86396d28c94523a6f6f00ae031432b
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188098B2

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