Benzenesulfonyl chloride → HCID 59540721, compound

HRID 1677510Notes

Reaction equation

HRID 1677510 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]3[C:16]([C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.C(N(C(C)C)CC)(C)C.[C:32]1([S:38](Cl)(=[O:40])=[O:39])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[OH-].[Na+]>C1COCC1.CC#N.O.ClCCl>[CH3:20][C:18]([CH3:19])([CH3:21])[C:17]([C:16]1[C:10]2[C:11](=[N:12][CH:13]=[C:8]([C:4]3[CH:3]=[C:2]([NH:1][S:38]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)(=[O:40])=[O:39])[CH:7]=[CH:6][CH:5]=3)[N:9]=2)[NH:14][CH:15]=1)=[O:22]

Participants

9

Reactant 4

HCID 7369Benzenesulfonyl chloride2×HCID 14798Sodium HydroxideHCID 81531Diisopropylethylamine2×HCID 57829629HCID 57829629, compound

Product 1

HCID 59540721HCID 59540721, compoundYield 38%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To a flask was added 1-[2-(3-Amino-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one 0.027 gm (0.092 mM), 1 ml dichloromethane, diisopropylethylamine 0.040 ml (0.23 mM) and benzenesulfonyl chloride 0.026 ml (0.204 mM). The mixture was stirred over night. Additional benzenesulfonyl chloride 0.0095 ml (0.074 mM) and diisopropylethylamine 0.015 ml (0.086 mM) was added and the mixture stirred overnight. The mixture was concentrated, 10 ml water and a few drops 1 M hydrochloric acid were added and it was extracted with ethyl acetate (3×30 ml). The ethyl acetate was dried over magnesium sulfate, stripped and purified on a preparative TLC plate (35:65 ethyl acetate/hexane) to give the diadduct 0.035 gm (0.061 mM, 66% yield). The diadduct was dissolved in a mixture of 3 ml THF and 6 ml MeCN. To this was added 0.4 ml 3M aqueous sodium hydroxide and the mixture heated to 55° C. for 4 hours. To this was added 50 ml water and concentrated on a rotary evaporator to remove the THF and MeCN. To the mixture was added 1M hydrochloric acid till neutral (solid forms) and extracted with ethyl acetate (3×50 ml). The solution was dried over magnesium sulfate and purified by preparative TLC (50:50 ethyl acetate/hexane) to give N-{3-[7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl}-benzenesulfonamide 0.015 gm (0.035 mM, 38% overall yield) M+1 435, m.p. 217-219° C.

Workup

  1. stirringthe mixture stirred overnight
  2. concentrationThe mixture was concentrated
  3. addition10 ml water and a few drops 1 M hydrochloric acid were added
  4. extractionit was extracted with ethyl acetate (3×30 ml)
  5. dry with materialThe ethyl acetate was dried over magnesium sulfate
  6. custompurified on a preparative TLC plate (35:65 ethyl acetate/hexane)
  7. customto give the diadduct 0.035 gm (0.061 mM, 66% yield)
  8. concentrationconcentrated on a rotary evaporator
  9. customto remove the THF and MeCN
  10. additionTo the mixture was added 1M hydrochloric acid till neutral (solid forms)
  11. extractionextracted with ethyl acetate (3×50 ml)
  12. dry with materialThe solution was dried over magnesium sulfate
  13. custompurified by preparative TLC (50:50 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a0c44d2333ce4866b8fb1ad01445c589
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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