(R)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)prop-1-ene-2-sulfonyl chloride → (R)-N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)prop-1-ene-2-sulfonamide

HRID 929473Notes

Reaction equation

[CH3:1][C:2]1([CH3:14])[O:6][C@H:5]([CH2:7][C:8]([S:10](Cl)(=[O:12])=[O:11])=[CH2:9])[CH2:4][O:3]1.[F:15][C:16]1[C:21]([F:22])=[C:20]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([I:30])=[CH:26][C:25]=2[F:31])[C:19]([NH2:32])=[C:18]([O:33][CH3:34])[CH:17]=1>N1C=CC=CC=1>[F:22][C:21]1[C:20]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([I:30])=[CH:26][C:25]=2[F:31])=[C:19]([NH:32][S:10]([C:8]([CH2:7][C@@H:5]2[CH2:4][O:3][C:2]([CH3:14])([CH3:1])[O:6]2)=[CH2:9])(=[O:12])=[O:11])[C:18]([O:33][CH3:34])=[CH:17][C:16]=1[F:15]

Participants

Conditions

Temperature: 100 °C

Procedure

(R)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)prop-1-ene-2-sulfonyl chloride from STEP C was dissolved in pyridine (12 mL) and 5,6-difluoro-N1-(2-fluoro-4-iodophenyl)-3-methoxybenzene-1,2-diamine (2.56 g, 6.5 mmol) added. The solution was stirred at 100° C. for 2 hours and then partitioned with water and ethyl acetate. The organic layer was washed with brine, dried (MgSO4), concentrated under reduced pressure and purified by flash column chromatography on silica (30% ethyl acetate/hexanes eluant) to afford (R)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)prop-1-ene-2-sulfonamide (651 mg, 17%).

Workup

custompartitioned with water and ethyl acetate
washThe organic layer was washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated under reduced pressure
custompurified by flash column chromatography on silica (30% ethyl acetate/hexanes eluant)

Sources & evidence

ORD record: ord-a1180df50b6e406eb027f5df06e1cdee
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296686B2

Reaction notes

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