Hydrochloric Acid → 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (R)-sec-butyl ester

HRID 1931710

Reaktionsgleichung

Reaktionsgleichung von HRID 1931710
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[CH3:13][C@@H:14]([OH:17])[CH2:15][CH3:16].N1C=CC=CC=1.Cl.FC(F)(F)C(O)=O.[CH3:32][S:33]([C:36]1[CH:57]=[CH:56][C:39]([O:40][C:41]2[N:46]=[CH:45][N:44]=[C:43]3[N:47]([CH:50]4[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]4)[N:48]=[CH:49][C:42]=23)=[CH:38][CH:37]=1)(=[O:35])=[O:34].C(N(C(C)C)CC)(C)C>ClCCCl.O>[C@H:14]([O:17][C:2]([N:53]1[CH2:52][CH2:51][CH:50]([N:47]2[C:43]3=[N:44][CH:45]=[N:46][C:41]([O:40][C:39]4[CH:38]=[CH:37][C:36]([S:33]([CH3:32])(=[O:35])=[O:34])=[CH:57][CH:56]=4)=[C:42]3[CH:49]=[N:48]2)[CH2:55][CH2:54]1)=[O:4])([CH2:15][CH3:16])[CH3:13]

Komponenten

9

Edukt 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 81531DiisopropylethylamineHCID 84682(-)-2-ButanolHCID 94429TriphosgeneHCID 669153264-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Produkt 1

HCID 579648874-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (R)-sec-butyl esterAusbeute 36,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

Triphosgene (217 mg, 0.73 mmol) was added to a solution of (R)-(−)-2-butanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 148 mg, 2 mmol) in a mixture of pyridine (190 μL, 2.3 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 (3 mL) were added. The layers were separated and the organic phase was dried (magnesium sulfate), filtered, and evaporated. 4-(4-Methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 220 mg, 0.45 mmol) and diisopropylethylamine (250 μL) were added and the mixture was stirred for 30 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 (R)-sec-butyl ester (78 mg, 36%) as an off-white foam/solid.

Aufarbeitung

  1. temperaturecooled to room temperature
  2. customThe layers were separated
  3. dry with materialthe organic phase was dried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. stirringthe mixture was stirred for 30 min
  7. customchromatographed
  8. washeluting with 50-75% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-6176f9f9d84f4f64b679d351adaca44f
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188098B2

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