Water → 1-[(difluoromethyl)sulfonyl]-3-(4,6-dimethoxy-1,3,5-triazin-2-yl)-7-methoxy-1,3-dihydro-2H-indol-2-one

HRID 870292Notes

Reaction equation

HRID 870292 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([CH:11]2[C:19]3[C:14](=[C:15]([O:20][CH3:21])[CH:16]=[CH:17][CH:18]=3)[NH:13][C:12]2=[O:22])[N:4]=1.CN1C=CN=C1.[F:29][CH:30]([F:35])[S:31](Cl)(=[O:33])=[O:32].O>ClCCl>[F:29][CH:30]([F:35])[S:31]([N:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH3:21])[CH:11]([C:5]2[N:4]=[C:3]([O:2][CH3:1])[N:8]=[C:7]([O:9][CH3:10])[N:6]=2)[C:12]1=[O:22])(=[O:33])=[O:32]

Participants

6

Reactant 4

HCID 962WaterHCID 13901-Methylimidazole2×HCID 73932Difluoromethanesulphonyl chloride2×HCID 679824623-(4,6-dimethoxy-1,3,5-triazin-2-yl)-7-methoxy-1,3-dihydro-2H-indol-2-one

Product 1

HCID 574047351-[(difluoromethyl)sulfonyl]-3-(4,6-dimethoxy-1,3,5-triazin-2-yl)-7-methoxy-1,3-dihydro-2H-indol-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

3-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-7-methoxy-1,3-dihydro-2H-indol-2-one (1.0 g) and 1-methyl-1H-imidazole (0.47 g) are introduced as initial charge in 8 ml of dichloromethane and cooled to −15° C. with nitrogen. With stirring, difluoromethanesulfonyl chloride (0.62 g) is added dropwise in two portions and the mixture is heated to 10° C. in 2.5 hours. It is cooled to 0° C., 1-methyl-1H-imidazole (0.24 g) and difluoromethanesulfonyl chloride (0.35 g) are added, and the mixture is warmed to room temperature over the course of 3 hours, after-stirred for 4 hours and left to stand for 48 hours. For work-up, water is added and the mixture is stirred, and the solid is filtered off, washed with dilute hydrochloric acid and water and dried. This gives the title compound as a solid in an HPLC purity of 91% (0.52 g, 39% of theory). The UV absorption (maximum at 360 nm) verifies the N-sulfonylation of the product.

Workup

  1. temperaturethe mixture is heated to 10° C. in 2.5 hours
  2. temperatureIt is cooled to 0° C.
  3. temperaturethe mixture is warmed to room temperature over the course of 3 hours
  4. stirringafter-stirred for 4 hours
  5. waitleft
  6. stirringthe mixture is stirred
  7. filtrationthe solid is filtered off
  8. washwashed with dilute hydrochloric acid and water
  9. customdried

Sources & evidence

ORD record
ord-212401ef03964f23bfc03565a125033b
Source dataset
uspto-grants-2015_03
Patent number
US08969553B2

Reaction notes

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