Reacción #1702056

Ecuación de reacción

4-[(1R,3S)-3-[[(1R)-1-(4-fluoro-3-methoxy-phenyl)ethyl]amino]cyclopentyl]benzonitrile

trimethylsilylazide

→

title compound

(1S,3R)—N-[(1R)-1-(4-fluoro-3-methoxy-phenyl)ethyl]-3-[4-(1H-tetrazol-5-yl)phenyl]cyclopentanamine

Disolventes

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITION9.5 ml, 72 mmol, dropwise addition)
2. 2
   FiltraciónThe precipitate was filtered off
3. 3
   Otrothe filtrate was evaporated
4. 4
   Otropurified by flash chromatography (gradient of 0-10%, MeOH in DCM containing 2% NEt3)
5. 5
   OtroThe product thus obtained
6. 6
   Otrowas precipitated from EtOH
7. 7
   workup.DISSOLUTIONredissolved in DCM
8. 8
   Extracciónextracted with aqueous HCl (pH 1)
9. 9
   Filtraciónthe resulting precipitate was filtered off
10. 10
    Otrodried

Procedimiento

4-[(1R,3S)-3-[[(1R)-1-(4-fluoro-3-methoxy-phenyl)ethyl]amino]cyclopentyl]benzonitrile (5.1 g, 14.4 mmol) in toluene (160 ml) was treated with trimethylsilylazide (9.5 ml, 72 mmol, dropwise addition) followed by SnBu2O (717 mg, 2.88 mmol). The reaction mixture was stirred at 118° C. overnight. The precipitate was filtered off, and the filtrate was evaporated and purified by flash chromatography (gradient of 0-10%, MeOH in DCM containing 2% NEt3). The product thus obtained was precipitated from EtOH, redissolved in DCM and extracted with aqueous HCl (pH 1). The aqueous phase was neutralized to pH 5-6 with NaOH aq. (1M), and the resulting precipitate was filtered off and dried to afford the title compound. 1H NMR (300 MHz, DMSO) δ 7.89 (d, J=8.2 Hz, 2H), 7.39 (dd, J=8.3, 1.8 Hz, 1H), 7.33-7.23 (m, 3H), 7.14-7.03 (m, 1H), 4.38 (q, J=6.5 Hz, 1H), 3.86 (s, 3H), 3.45-3.32 (m, 1H), 3.09-2.95 (m, 1H), 2.38-2.25 (m, 1H), 2.10-1.64 (m, 5H), 1.56 (d, J=6.7 Hz, 3H).

Fuente