2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 2-(3-Sulfamoyl-phenylamino)-thieno[2,3-h]quinazoline-8-carboxylic acid tert-butyl ester

HRID 643741Notes

Reaction equation

HRID 643741 reaction equation
[C:1]([O:5][C:6]([C:8]1[S:31][C:11]2[CH2:12][CH2:13][C:14]3[CH:15]=[N:16][C:17]([NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([S:27](=[O:30])(=[O:29])[NH2:28])[CH:22]=4)=[N:18][C:19]=3[C:10]=2[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>O1CCOCC1>[C:1]([O:5][C:6]([C:8]1[S:31][C:11]2=[CH:12][CH:13]=[C:14]3[C:19]([N:18]=[C:17]([NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([S:27](=[O:29])(=[O:30])[NH2:28])[CH:22]=4)[N:16]=[CH:15]3)=[C:10]2[CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 592628022-(3-Sulfamoyl-phenylamino)-5,6-dihydro-thieno[2,3-h] quinazoline-8-carboxylic acid tert-butyl ester

Product 1

HCID 592628832-(3-Sulfamoyl-phenylamino)-thieno[2,3-h]quinazoline-8-carboxylic acid tert-butyl esterYield 38%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2-(3-Sulfamoyl-phenylamino)-5,6-dihydro-thieno[2,3-h]quinazoline-8-carboxylic acid tert-butyl ester (4.90 g, 10.69 mmol) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (4.85 g, 21.37 mmol) were suspended in dry 1,4-dioxane (300 mL) and heated at reflux overnight. After allowing the reaction to cool to room temperature the mixture was concentrated under reduced pressure and partitioned between ethyl acetate and 1:1 saturated Na2CO3:brine. The organic layer was washed with further portions of 1:1 saturated Na2CO3:brine (2×200 mL), dried over Na2SO4, and filtered. Silica (˜60 mL) was added to the filtrate and the resulting suspension was concentrated under reduced pressure. The resulting solid was purified by silica gel chromatography (80-90% EtOAc in hexanes on ˜800 mL of silica) to afford the title compound as a yellow solid (1.84 g, 38% yield) and further impure material (˜2 g). MS (ES+) 457. δH (d6 DMSO) 1.6 (9H, s), 7.3 (2H, br s), 7.4-7.6 (2H, m), 7.8-7.9 (1H, m), 8.0 (2H, m), 8.7 (1H, s), 9.1 (1H, br s), 9.4 (1H, s), 10.4-10.5 (1H, s).

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. customthe reaction
  4. concentrationwas concentrated under reduced pressure
  5. custompartitioned between ethyl acetate and 1:1 saturated Na2CO3
  6. washThe organic layer was washed with further portions of 1:1 saturated Na2CO3
  7. dry with materialbrine (2×200 mL), dried over Na2SO4
  8. filtrationfiltered
  9. additionSilica (˜60 mL) was added to the filtrate
  10. concentrationthe resulting suspension was concentrated under reduced pressure
  11. customThe resulting solid was purified by silica gel chromatography (80-90% EtOAc in hexanes on ˜800 mL of silica)

Sources & evidence

ORD record
ord-a80d45acad9b459f860dc10635b97858
Source dataset
uspto-grants-2010_04
Patent number
US07700609B2

Reaction notes

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