反応 #1702056

反応方程式

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

溶媒

toluene

反応条件

後処理

1. 1
   workup.ADDITION9.5 ml, 72 mmol, dropwise addition)
2. 2
   ろ過The precipitate was filtered off
3. 3
   その他the filtrate was evaporated
4. 4
   その他purified by flash chromatography (gradient of 0-10%, MeOH in DCM containing 2% NEt3)
5. 5
   その他The product thus obtained
6. 6
   その他was precipitated from EtOH
7. 7
   workup.DISSOLUTIONredissolved in DCM
8. 8
   抽出extracted with aqueous HCl (pH 1)
9. 9
   ろ過the resulting precipitate was filtered off
10. 10
    その他dried

実験手順

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).

出典