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

HRID 634262Notes

Reaction equation

HRID 634262 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:15]=[C:14]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[S:13][N:12]=3)[CH:9]=2)[NH:4][CH:3]=1.[H-].[Na+].[CH3:26][C:27]1[CH:32]=[CH:31][C:30]([S:33](Cl)(=[O:35])=[O:34])=[CH:29][CH:28]=1>CN(C=O)C>[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:15]=[C:14]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:22])[CH3:21])[S:13][N:12]=3)[CH:9]=2)[N:4]([S:33]([C:30]2[CH:31]=[CH:32][C:27]([CH3:26])=[CH:28][CH:29]=2)(=[O:35])=[O:34])[CH:3]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 68356843tert-butyl 3-(3-iodo-1H-indol-5-yl)-1,2,4-thiadiazol-5-ylcarbamate

Product 1

HCID 86725113tert-butyl 3-(3-iodo-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-ylcarbamateYield 46.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-80accd7e18bb425db67b55084093c550
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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