Sulfuryl chloride → HCID 46195835, compound

HRID 881651Notes

Reaction equation

HRID 881651 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([O:8][C:9]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=3[F:27])[C:10]=2[C:11]([NH2:13])=[O:12])[CH:5]=[N:6][CH:7]=1.[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:18][C:16]1[CH:17]=[C:9]([O:8][C:4]2[CH:5]=[N:6][CH:7]=[C:2]([NH:1][S:31]([CH:28]([CH3:30])[CH3:29])(=[O:33])=[O:32])[CH:3]=2)[C:10]([C:11]([NH2:13])=[O:12])=[C:14]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=2[F:27])[CH:15]=1

Participants

6

Reactant 3

HCID 24648Sulfuryl chloride2×HCID 824082-Propanesulfonyl chlorideHCID 66919498HCID 66919498, compound2×

Product 1

HCID 46195835HCID 46195835, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

In analogy to GP 6b, 100 mg of 2-(5-Amino-pyridin-3-yloxy)-4-fluoro-6-(2-fluoro-4-iodo-phenylamino)-benzamide (Intermediate 3.1; 0.21 mmol, 1 eq.) were dissolved in 1.5 mL pyridine and treated with 37 mg iso-propylsulfonyl chloride (0.26 mmol, 1.25 eq., dissolved in 0.5 mL pyridine). The reaction mixture was stirred at rt overnight, treated with another 1.25 eq. sulfonylchloride (in 0.2 mL pyridine) and stirring was continued at rt overnight. After addition of further 1.25 eq. sulfonylchloride (in 0.2 mL pyridine) and further stirring at rt for 3 days, the resulting mixture diluted with ethyl acetate, washed with water and the organic layers dried. Concentration in vacuo was followed by prepurification by chromatography and subsequent HPLC purification to provide the desired compound.

Workup

  1. stirringstirring
  2. waitwas continued at rt overnight
  3. stirringfurther stirring at rt for 3 days
  4. washwashed with water
  5. customthe organic layers dried
  6. concentrationConcentration in vacuo
  7. customwas followed by prepurification by chromatography and subsequent HPLC purification

Sources & evidence

ORD record
ord-0d5bb575df82462088818c7e7a5d404c
Source dataset
uspto-grants-2015_03
Patent number
US08993630B2

Reaction notes

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