Reaktion #2286961

Reaktionsgleichung

{(R)-1-[4-cyano-5-(pyridin-2-ylamino)-thiazol-2-yl]-piperidin-3-yl}-carbamic acid tert-butyl ester

tetrahydrofuran water

→

{(R)-1-[4-carbamoyl-5-(pyridin-2-ylamino)-thiazol-2-yl]-piperidin-3-yl}-carbamic acid tert-butyl ester

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeby bubbling in argon for 10 minutes
2. 2
   TemperaturThe reaction mixture was cooled to ambient temperature
3. 3
   Extraktionextracted with 1:1 v/v tetrahydrofuran/ethyl acetate (4×50 mL)
4. 4
   Waschenthe combined organic extracts were washed with brine (2×40 mL)
5. 5
   Trocknendried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo to a yellow solid
8. 8
   SonstigeThe crude product was purified by chromatography
9. 9
   Wascheneluted from 30% up to 70% v/v ethyl acetate in hexanes
10. 10
    workup.ADDITIONThe product containing fractions
11. 11
    Einengenconcentrated in vacuo

Vorschrift

A solution of {(R)-1-[4-cyano-5-(pyridin-2-ylamino)-thiazol-2-yl]-piperidin-3-yl}-carbamic acid tert-butyl ester (455 mg, 1.14 mmol) in 10:1 v/v tetrahydrofuran/water (16.5 mL total volume) was degassed by bubbling in argon for 10 minutes with stiffing. Hydrido-(dimethylphosphinous acid-kP)[hydrogen bis(dimethylphosphnito-kP]platinum (II) (CAS number 173416-05-2) (78 mg, 183 μmol) was added and the mixture was heated to 150° C. by microwave for 45 minutes. The reaction mixture was cooled to ambient temperature, poured into water (150 mL) and extracted with 1:1 v/v tetrahydrofuran/ethyl acetate (4×50 mL), the combined organic extracts were washed with brine (2×40 mL), dried over sodium sulfate, filtered and concentrated in vacuo to a yellow solid. The crude product was purified by chromatography using silica gel gradient eluted from 30% up to 70% v/v ethyl acetate in hexanes. The product containing fractions were combined and concentrated in vacuo to obtain {(R)-1-[4-carbamoyl-5-(pyridin-2-ylamino)-thiazol-2-yl]-piperidin-3-yl}-carbamic acid tert-butyl ester as an off white solid (362 mg, 76%). LC/MS: m/z calculated for C19H26N6O3S ([M−H]−): 417.5. Found: 417.4 (negative mode electrospray ionization).

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