تفاعل #1885049

معادلة التفاعل

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

المردود 29.5%

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

المردود 29.5%

المذيبات

acetonitrile

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىSynthesized
2. 2
   workup.ADDITIONTo this was slowly added
3. 3
   workup.STIRRINGthe reaction mixture was stirred at 0° C. for 15 min
4. 4
   أخرىthe 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
   استخلاصextracted with EtOAc (3×)
8. 8
   غسيلThe combined organic extracts were washed with brine
9. 9
   تجفيفdried over Na2SO4
10. 10
    أخرىevaporated to dryness
11. 11
    أخرىPurification by silica gel chromatography (0-10% MeOH in EtOAc)

الإجراء التجريبي

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.

المصدر