Sulfuryl chloride → HCID 46195697, compound

HRID 881650Notes

Reaction equation

HRID 881650 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][CH:27]=1)[O:5][C:6]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])[C:7]=1[C:8]([NH2:10])=[O:9].[CH:28]([S:31](Cl)(=[O:33])=[O:32])([CH3:30])[CH3:29].S(Cl)(Cl)(=O)=O>N1C=CC=CC=1.C(OCC)(=O)C>[F:15][C:13]1[CH:14]=[C:6]([O:5][C:4]2[CH:25]=[CH:26][CH:27]=[C:2]([NH:1][S:31]([CH:28]([CH3:30])[CH3:29])(=[O:33])=[O:32])[CH:3]=2)[C:7]([C:8]([NH2:10])=[O:9])=[C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])[CH:12]=1

Participants

6

Reactant 3

HCID 24648Sulfuryl chloride2×HCID 824082-Propanesulfonyl chlorideHCID 57624911HCID 57624911, compound2×

Product 1

HCID 46195697HCID 46195697, compoundYield 46.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

In analogy to GP 6b, 144 mg of 2-(3-amino-phenoxy)-4-fluoro-6-(2-fluoro-4-iodo-phenylamino)-benzamide (Intermediate 1.4; 0.3 mmol, 1 eq.) were dissolved in 1.5 mL pyridine and treated with 51 mg iso-propylsulfonyl chloride (0.36 mmol, 1.2 eq., dissolved in 0.5 mL pyridine). The reaction mixture was stirred at rt overnight, treated with another 0.5 eq. sulfonylchloride (in 0.2 mL pyridine) and stirring was continued at rt overnight. After addition of further 0.5 eq. sulfonylchloride (in 0.2 mL pyridine) and further stirring at rt overnight, the resulting mixture diluted with ethyl acetate, washed with water and the organic layers dried. Concentration in vacuo followed by HPLC purification provided 82 mg (46% yield) of the desired compound, which includes substoichiometric amounts of formic acid.

Workup

  1. stirringstirring
  2. waitwas continued at rt overnight
  3. stirringfurther stirring at rt overnight
  4. washwashed with water
  5. customthe organic layers dried
  6. concentrationConcentration in vacuo
  7. customfollowed by HPLC purification

Sources & evidence

ORD record
ord-42f303b8f51f4c9ea31b8a7b11c41ccb
Source dataset
uspto-grants-2015_03
Patent number
US08993630B2

Reaction notes

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