반응 #1885049

반응 방정식

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

수율 29.5%

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

수율 29.5%

용매

acetonitrile

acetonitrile

반응 조건

후처리

1. 1
   기타Synthesized
2. 2
   workup.ADDITIONTo this was slowly added
3. 3
   workup.STIRRINGthe reaction mixture was stirred at 0° C. for 15 min
4. 4
   기타the 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
   추출extracted with EtOAc (3×)
8. 8
   세척The combined organic extracts were washed with brine
9. 9
   건조dried over Na2SO4
10. 10
    기타evaporated to dryness
11. 11
    기타Purification by silica gel chromatography (0-10% MeOH in EtOAc)

실험 절차

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.

출처