Reacción #1885049

Ecuación de reacción

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

Rendimiento 29.5%

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

Rendimiento 29.5%

Disolventes

acetonitrile

acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroSynthesized
2. 2
   workup.ADDITIONTo this was slowly added
3. 3
   workup.STIRRINGthe reaction mixture was stirred at 0° C. for 15 min
4. 4
   Otrothe 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
   Extracciónextracted with EtOAc (3×)
8. 8
   LavadoThe combined organic extracts were washed with brine
9. 9
   Secadodried over Na2SO4
10. 10
    Otroevaporated to dryness
11. 11
    OtroPurification by silica gel chromatography (0-10% MeOH in EtOAc)

Procedimiento

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.

Fuente