Ethyl isocyanate → HCID 86704197, compound

HRID 1497657Notes

Reaction equation

HRID 1497657 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)=[C:5]([C:7]2[C:8]([F:29])=[C:9]([N:14]([CH2:26][O:27][CH3:28])[S:15]([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])(=[O:17])=[O:16])[CH:10]=[CH:11][C:12]=2[F:13])[N:6]=1.[CH2:36]([N:38]=[C:39]=[O:40])[CH3:37]>O1CCOCC1>[CH2:36]([NH:38][C:39]([NH:1][C:2]1[S:3][C:4]([C:30]2[CH:31]=[CH:32][N:33]=[CH:34][CH:35]=2)=[C:5]([C:7]2[C:8]([F:29])=[C:9]([N:14]([CH2:26][O:27][CH3:28])[S:15]([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])(=[O:17])=[O:16])[CH:10]=[CH:11][C:12]=2[F:13])[N:6]=1)=[O:40])[CH3:37]

Participants

4

Reactant 2

HCID 8022Ethyl isocyanateHCID 86704198HCID 86704198, compound

Product 1

HCID 86704197HCID 86704197, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

N-{3-[2-amino-5-(pyridin-4-yl)-1,3-thiazol-4-yl]-2,4-difluorophenyl}-2,5-difluoro-N-(methoxymethyl)benzenesulfonamide (prepared as described in Example 3, 50 mg, 0.1 mmol) was dissolved in 2 mL of dry 1,4-dioxane and a total amount of 320 μL (4 mmol) of ethylisocyanate were added portionwise until the reaction was complete. The solution was heated at 80° C. under stirring for 18 h. The solvent was then removed and the residue taken up with DCM and washed with water. The organic phase was dried over Na2SO4 and evaporated to dryness, giving N-(3-{2-[(ethylcarbamoyl)amino]-5-(pyridin-4-yl)-1,3-thiazol-4-yl}-2,4-difluorophenyl)-2,5-difluoro-N-(methoxymethyl)benzenesulfonamide. The latter, without any further purification, was dissolved in 9 mL of TFA and 1 mL of water and the resulting mixture was maintained at 60° C. under stirring for 8 h. The solvent was evaporated and the residue taken up with DCM and washed with aqueous NaHCO3. The organic layer was then dried over Na2SO4 and evaporated again. The product was purified by flash chromatography on a silica gel precoated column eluted with DCM-MeOH 95/5, affording, after trituration with diethylether-diisopropyl ether, 17 mg (31%) of the title compound.

Workup

  1. customThe solvent was then removed
  2. washwashed with water
  3. dry with materialThe organic phase was dried over Na2SO4
  4. customevaporated to dryness

Sources & evidence

ORD record
ord-e96986dc72cc42d0b010c54162f5dbf5
Source dataset
uspto-grants-2015_12
Patent number
US09199979B2

Reaction notes

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