4-Toluenesulfonyl chloride → tert-butyl 3-(3-iodo-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-ylcarbamate

To a solution of tert-butyl (3-(3-iodo-1H-indol-5-yl)-1,2,4-thiadiazol-5-yl)carbamate (80 mg, 0.18 mmol) in DMF (2.5 mL) at 0° C. was added 60% NaH (80 mg, 0.199 mmol) at 0° C. and the reaction was stirred at RT. After 5 min, the mixture was again cooled to 0° C. and 4-methylbenzene sulfonyl chloride (38 mg, 0.199 mmol) in DMF (2.5 mL) was added dropwise. The reaction was stirred at RT for 1 h, then treated with ice cold water (5 mL) and extracted with EtOAc (10 mL). The aqueous layer was back extracted with EtOAc (10 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated. The crude was purified by silica-gel column Chromatography (eluent: 15% EtOAc in petroleum ether) to give tert-butyl (3-(3-iodo-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-yl)carbamate (50 mg, 46.7%) as an off white solid. MS (ESI, pos. ion) m/z: 540.9 (M+1) (carbamic acid mass). 1H NMR (400 MHz, DMSO-d6) δ 12.45 (brs, 1H), 8.22-8.19 (m, 1H), 8.15 (s, 1H), 8.11-8.07 (m, 2H), 7.95 (d, J=8.4 Hz, 2H), 7.41 (d, J=8 Hz, 2H), 2.31 (s, 3H), 1.51 (s, 9H).

1. temperaturethe mixture was again cooled to 0° C.
2. stirringThe reaction was stirred at RT for 1 h
3. extractionextracted with EtOAc (10 mL)
4. extractionThe aqueous layer was back extracted with EtOAc (10 mL)
5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
6. concentrationconcentrated
7. customThe crude was purified by silica-gel column Chromatography (eluent: 15% EtOAc in petroleum ether)

ORDレコード

ord-80accd7e18bb425db67b55084093c550

出典データセット

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09321756B2