Reaktion #92025

Reaktionsgleichung

sodium borohydride

TFA

(S)-2-(4-cyano-2,6-difluoro-benzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl)-phenyl]-propionic acid propyl ester

isopropyl alcohol

→

(S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid propyl ester

Ausbeute 74.5%

Lösungsmittel

THF

isopropyl acetate

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschendrop wise (flask was rinsed w/THF (2×1 ml) and added to reaction)
2. 2
   workup.STIRRINGThe reaction was stirred at room temperature under nitrogen for 1.3 h
3. 3
   TemperaturThe reaction mixture was cooled in an ice bath
4. 4
   Sonstigequenched with water (20 ml)
5. 5
   ExtraktionThe aqueous mixture was extracted with DCM (2×200 ml)
6. 6
   Waschenthe organic layers were washed with brine
7. 7
   Trocknendried over magnesium sulfate
8. 8
   Einengenconcentrated
9. 9
   Sonstigeto yield an off white solid, 1.77 g
10. 10
    workup.STIRRINGThe reaction was stirred at room temperature for 2 h
11. 11
    Filtrationthe white precipitate was filtered
12. 12
    Waschenwashed with isopropyl acetate and hexanes

Vorschrift

To solution of sodium borohydride (0.29 g, 7.62 mmol, 2 eq.) in THF (5 ml) was added TFA (566 μL, 7.62 mmol, 2 eq.), the reaction was stirred for 10 min., and then a solution of (S)-2-(4-cyano-2,6-difluoro-benzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl)-phenyl]-propionic acid propyl ester (2.0 g, 3.81 mmol) in THF (6 ml) was added drop wise (flask was rinsed w/THF (2×1 ml) and added to reaction). The reaction was stirred at room temperature under nitrogen for 1.3 h. The reaction mixture was cooled in an ice bath and quenched with water (20 ml) and a sodium chloride solution (20 ml water, 100 ml saturated solution). The aqueous mixture was extracted with DCM (2×200 ml), and then the organic layers were washed with brine, combined, and dried over magnesium sulfate, and then concentrated to yield an off white solid, 1.77 g. The crude product was suspended in isopropyl acetate (75 ml) and isopropyl alcohol (0.75 ml and TMSC1 (1 ml) was added dropwise. The reaction was stirred at room temperature for 2 h and the white precipitate was filtered and washed with isopropyl acetate and hexanes to obtain 1.5 g (63% yield) of (S)-2-(4-aminomethyl-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid propyl ester as an amorphous white solid. ES-HRMS m/e calcd for C27H30F2N4O5 (M+H)+ 529.2257, found 529.2258.

Quelle