反応 #1885049

反応方程式

4-[(3R,3′S)-3-(3,5-dichlorophenyl)-2′-oxo-1,3′-bipyrrolidin-1′-yl]benzene-1-sulfonyl chloride

2-aminothiazole

2-tert-butyl-1,1,3,3-tetramethylguanidine

→

desired product

収率 29.5%

4-[(3R,3′S)-3-(3,5-Dichlorophenyl)-2′-oxo-1,3′-bipyrrolidin-1′-yl]-N-(thiazol-2-yl)benzenesulfonamide

収率 29.5%

溶媒

acetonitrile

acetonitrile

反応条件

後処理

1. 1
   その他Synthesized
2. 2
   workup.ADDITIONTo this was slowly added
3. 3
   workup.STIRRINGthe reaction mixture was stirred at 0° C. for 15 min
4. 4
   その他the cooling bath was removed
5. 5
   workup.STIRRINGthe reaction mixture was stirred at RT for 30 min
6. 6
   workup.ADDITIONThe reaction mixture was then poured into water
7. 7
   抽出extracted with EtOAc (3×)
8. 8
   洗浄The combined organic extracts were washed with brine
9. 9
   乾燥dried over Na2SO4
10. 10
    その他evaporated to dryness
11. 11
    その他Purification by silica gel chromatography (0-10% MeOH in EtOAc)

実験手順

Synthesized according to General Procedure 12, Method B: To a stirred solution of 2-aminothiazole (88.8 mg, 0.89 mmol) in acetonitrile (1 mL) at 0° C. was added 2-tert-butyl-1,1,3,3-tetramethylguanidine (152 mg, 0.89 mmol) dropwise and the reaction mixture was stirred at 0° C. for 15 min. To this was slowly added a suspension of 4-[(3R,3′S)-3-(3,5-dichlorophenyl)-2′-oxo-1,3′-bipyrrolidin-1′-yl]benzene-1-sulfonyl chloride (100 mg, 0.17 mmol) in acetonitrile (0.5 mL) and the reaction mixture was stirred at 0° C. for 15 min, the cooling bath was removed and the reaction mixture was stirred at RT for 30 min. The reaction mixture was then poured into water, the pH was adjusted to ˜7 with 1M HCl, and extracted with EtOAc (3×). The combined organic extracts were washed with brine, dried over Na2SO4 and evaporated to dryness. Purification by silica gel chromatography (0-10% MeOH in EtOAc) afforded the desired product as a solid (27 mg, 28%). 1H-NMR (400 MHz, DMSO-d6) δ 7.84-7.77 (m, 4H), 7.43-7.37 (m, 3H), 7.24 (d, J=4.6 Hz, 1H), 6.81 (d, J=4.6 Hz, 1H), 3.83-3.72 (m, 2H), 3.58 (t, J=8.8 Hz, 1H), 3.07-2.96 (m, 3H), 2.87 (td, J=8.6, 4.3 Hz, 1H), 2.34-2.20 (m, 2H), 2.11-2.02 (m, 1H) and 1.74 (dt, J=19.9, 6.9 Hz, 1H) ppm. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=537.3; tR=1.21 min.

出典