反応 #1800940

反応方程式

Hydrazine monohydrate

Methyl chloro(oxo)acetate

HCl

2-Fluorophenylisothiocyanate

EDAC

di-isopropylethylamine

Methyl 4-(4-aminophenyl)butanoate

→

title compound

収率 44.0%

Methyl 4-{4-[({5-[(2-fluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]phenyl}butanoate

収率 44.0%

溶媒

DMF

DCM

DCM

反応条件

後処理

1. 1
   ろ過was filtered off
2. 2
   洗浄washed with DCM (3 mL)
3. 3
   その他a white precipitate formed after 2 h
4. 4
   workup.STIRRINGThe reaction mixture was stirred at room temperature overnight
5. 5
   workup.DISSOLUTIONto dissolve the solid
6. 6
   workup.STIRRINGthe mixture stirred at room temperature for 2.5 h
7. 7
   workup.STIRRINGAfter stirring at room temperature for a further 2.5 h the mixture
8. 8
   温度was heated to 50° C.
9. 9
   その他to evaporate
10. 10
    workup.WAITAfter 2 h the reaction had gone to completion
11. 11
    濃縮the mixture was concentrated in vacuo
12. 12
    その他The orange solid obtained
13. 13
    その他was crystallised from water
14. 14
    ろ過filtered
15. 15
    洗浄The solid was then washed with Et2O, EtOAc

実験手順

Methyl 4-(4-aminophenyl)butanoate (Journal of Medicinal Chemistry (1990), 33(11), 3014-19) (193 mg, 1 mmol) was stirred in dry DCM (9 mL) and PS-di-isopropylethylamine (750 mg, 3 mmol) was added. Methyl chloro(oxo)acetate (101 μl, 1.1 mmol) was added to the reaction mixture which was then stirred at room temperature for 2 h. The polymer supported base (HCl salt) was filtered off and washed with DCM (3 mL). Hydrazine monohydrate (53 μL, 1.1 mmol) was added to the stirred filtrate and a white precipitate formed after 2 h. The reaction mixture was stirred at room temperature overnight then DMF (5 mL) was added to dissolve the solid. 2-Fluorophenylisothiocyanate (0.135 mL, 1.1 mmol) was added via a pipette and the mixture stirred at room temperature for 2.5 h before adding EDAC (230 mg, 1.2 mmol). After stirring at room temperature for a further 2.5 h the mixture was heated to 50° C. and the DCM was allowed to evaporate. After 2 h the reaction had gone to completion and the mixture was concentrated in vacuo. The orange solid obtained was crystallised from water and then filtered. The solid was then washed with Et2O, EtOAc and then MeCN (1 mL) to give the title compound (174 mg, 44%) as a solid; 1H NMR δ 1.79-1.87 (2H, m), 2.31 (2H, t), 2.58 (2H, t), 3.59 (3H, s), 7.15-7.20 (3H, m), 7.25-7.34 (2H, m), 7.71 (2H, d), 8.02-8.07 (1H, m), 10.76 (1H, s), 10.95 (1H, s); MS m/e MH+ 399.

出典