Hydrochloric Acid → 3-(4,6-diethoxy-1,3,5-triazin-2-yl)-1-[(difluoromethyl)sulfonyl]-7-fluoro-1,3-dihydro-2H-indol-2-one

HRID 870289Notes

Reaction equation

[CH2:1]([O:3][C:4]1[N:9]=[C:8]([O:10][CH2:11][CH3:12])[N:7]=[C:6]([CH:13]2[C:21]3[C:16](=[C:17]([F:22])[CH:18]=[CH:19][CH:20]=3)[NH:15][C:14]2=[O:23])[N:5]=1)[CH3:2].CN1C=CN=C1.[F:30][CH:31]([F:36])[S:32](Cl)(=[O:34])=[O:33].Cl>ClCCl.O>[CH2:11]([O:10][C:8]1[N:9]=[C:4]([O:3][CH2:1][CH3:2])[N:5]=[C:6]([CH:13]2[C:21]3[C:16](=[C:17]([F:22])[CH:18]=[CH:19][CH:20]=3)[N:15]([S:32]([CH:31]([F:36])[F:30])(=[O:34])=[O:33])[C:14]2=[O:23])[N:7]=1)[CH3:12]

Participants

Conditions

Temperature: 0 °C

Procedure

3-(4,6-Diethoxy-1,3,5-triazin-2-yl)-7-fluoro-1,3-dihydro-2H-indol-2-one (1.0 g) and 1-methyl-1H-imidazole (0.51 g) are introduced as initial charge in 10 ml of dichloromethane and cooled to 0° C. under nitrogen. With stirring, difluoromethanesulfonyl chloride (0.46 g) is added dropwise and the mixture is after-stirred for 2 hours at 0° C. to 6° C. After adding 1-methyl-1H-imidazole (0.25 g) and difluoromethanesulfonyl chloride (0.23 g), the mixture is stirred for 2 hours at 0° C. to 10° C. After adding 5 ml of water, the mixture is adjusted to pH 2 using 10% strength hydrochloric acid, the organic solvent is largely distilled off in vacuo, and the solid is filtered off, washed with water and heptane and dried. This gives the title compound as a solid in an HPLC purity of 93% (1.19 g, 83% of theory). The UV absorption (maximum at 360 nm) verifies the N-sulfonylation of the product.

Workup

stirringthe mixture is after-stirred for 2 hours at 0° C. to 6° C
stirringthe mixture is stirred for 2 hours at 0° C. to 10° C
distillationthe organic solvent is largely distilled off in vacuo
filtrationthe solid is filtered off
washwashed with water and heptane
customdried

Sources & evidence

ORD record: ord-5be7b2e09d654eb7bdac856355f569d2
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969553B2

Reaction notes

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