Dimethylformamide → HCID 72204793, compound

HRID 2204369Notes

Reaction equation

HRID 2204369 reaction equation
ClS([N:5]=[C:6]=O)(=O)=O.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH3:42])=[C:13]([N:15]2[C:22](=[O:23])[C:21]3[CH:20]=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[O:30][CH3:31])[N:18]([CH:32]([CH3:34])[CH3:33])[C:17]=3[CH:16]2[C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=2)[CH:14]=1.CN(C=O)C>CC#N>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH3:42])=[C:13]([N:15]2[C:22](=[O:23])[C:21]3[C:20]([C:6]#[N:5])=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[O:30][CH3:31])[N:18]([CH:32]([CH3:34])[CH3:33])[C:17]=3[CH:16]2[C:35]2[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][CH:40]=2)[CH:14]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 70918Chlorosulfonyl isocyanate2×HCID 72206099HCID 72206099, compound

Product 1

HCID 72204793HCID 72204793, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Chlorosulfonyl isocyanate [1189-71-5] (0.453 mmol) was added to a mixture of 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-2-(2-methoxy-phenyl)-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one (Example 9) (0.302 mmol) in CH3CN (2 mL) at 0° C. After stirring at rt for 2.5 h, additional chlorosulfonyl isocyanate (0.226 mmol) was added. After another 4 h, the reaction mixture was cooled to 0° C., treated with DMF (0.4 mL), stirred for 15 min and then warmed to 50° C. After 30 min, the reaction mixture was cooled to rt, poured onto ice-H2O and extracted with EtOAc. The organic layer was successively washed with a 1N aqueous solution of NaHCO3 and brine, dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel column chromatography to afford the title compound as an off-white solid. tR: 5.59 min (HPLC 1); ESI-MS: tR=1.39 min, [M+H]+ 530/532/534 (LC-MS 1); TLC: Rf=0.12 (1:3 EtOAc/heptanes); 1H-NMR (d6-DMSO, 600 MHz): (rotamers) 7.79/7.83 (s, 1H), 7.58 (m, 1H), 7.35-7.46 (m, 3H), 7.31 (m, 2H), 7.25 (m, 1H), 7.21 (m, 1H), 7.09-7.17 (m, 2H), 6.61 (s, 1H), 3.97/4.01 (m, 1H), 3.77/3.83 (s, 3H), 1.93 (s, 3H), 1.26/1.35 (m, 3H), 0.42/0.58 (m, 3H).

Workup

  1. waitAfter another 4 h
  2. temperaturethe reaction mixture was cooled to 0° C.
  3. stirringstirred for 15 min
  4. temperaturewarmed to 50° C
  5. waitAfter 30 min
  6. temperaturethe reaction mixture was cooled to rt
  7. additionpoured onto ice-H2O
  8. extractionextracted with EtOAc
  9. washThe organic layer was successively washed with a 1N aqueous solution of NaHCO3 and brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-659b801131bf4c12921e55bbf0284f30
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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