Реакция #1702056

Уравнение реакции

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

Растворители

toluene

Условия реакции

Обработка

1. 1
   workup.ADDITION9.5 ml, 72 mmol, dropwise addition)
2. 2
   ФильтрацияThe precipitate was filtered off
3. 3
   Другоеthe filtrate was evaporated
4. 4
   Другоеpurified by flash chromatography (gradient of 0-10%, MeOH in DCM containing 2% NEt3)
5. 5
   ДругоеThe product thus obtained
6. 6
   Другоеwas precipitated from EtOH
7. 7
   workup.DISSOLUTIONredissolved in DCM
8. 8
   Экстракцияextracted with aqueous HCl (pH 1)
9. 9
   Фильтрацияthe resulting precipitate was filtered off
10. 10
    Другоеdried

Методика

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).

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