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(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 1895536
Notes
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Reaction equation

HRID 1895536 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 50914395(R)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)prop-1-ene-2-sulfonyl chlorideHCID 532609665,6-difluoro-N1-(2-fluoro-4-iodophenyl)-3-methoxybenzene-1,2-diamine

Product 1

HCID 86667893(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-sulfonamideYield 17%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

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

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

Sources & evidence

ORD record
ord-b5a3e35b18c6430f857cb6ffb8586bf9
Source dataset
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08513443B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes