Thionyl Chloride → HCID 58086051, compound

HRID 1261075Notes

Reaction equation

HRID 1261075 reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].[Br:5][C:6]1[CH:7]=[C:8]2[C:12](=[N:13][CH:14]=1)[NH:11][CH:10]=[CH:9]2.[CH2:15]([NH:19][C:20](=[O:32])[NH:21][C:22]1[CH:23]=[CH:24][C:25]([F:31])=[C:26]([CH:30]=1)[C:27](O)=[O:28])[CH2:16][CH2:17][CH3:18].S(Cl)(Cl)=O>ClCCl.O1CCCC1.CN(C)C=O>[Br:5][C:6]1[CH:7]=[C:8]2[C:9]([C:27]([C:26]3[CH:30]=[C:22]([NH:21][C:20]([NH:19][CH2:15][CH2:16][CH2:17][CH3:18])=[O:32])[CH:23]=[CH:24][C:25]=3[F:31])=[O:28])=[CH:10][NH:11][C:12]2=[N:13][CH:14]=1

Participants

8

Reactant 4

HCID 24386Thionyl Chloride2×HCID 6451240Aluminum(III) ChlorideHCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridineHCID 58086811HCID 58086811, compound

Product 1

HCID 58086051HCID 58086051, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

To aluminum trichloride (0.524 g, 0.00393 mol) and dichloromethane (20 mL, 0.3 mol) under an atmosphere of nitrogen was added 5-bromo-7-azaindole (67, 0.155 g, 0.000787 mol) in dichloromethane. To 5-(3-butylureido)-2-fluorobenzoic acid (588, 0.200 g, 0.000787 mol) was added 4 mL of dichloromethane (4 mL) followed by thionyl chloride (69 μL, 0.00094 mol) and a drop of N,N-dimethylformamide. After 1 hour, the reaction remained a suspension so additional thionyl chloride was added along with tetrahydrofuran. The reaction remained a suspension, so was placed in a 50° C. oil bath. After another hour, the reaction was still a suspension, and so was left to react at 50° C. overnight. The reaction had become a clear solution. All volatiles were removed under vacuum, then the residue dissolved in dichloromethane and added to the 5-bromo-7-azaindole and aluminum trichloride suspension. The reaction was allowed to stir at room temperature for 4.5 hours, followed by the addition of water and extraction with ethyl acetate. The organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with a gradient of methanol (0 to 10%) in dichloromethane to give the compound (P-1637, 14 mg, 4%).

Workup

  1. customso was placed in a 50° C.
  2. waitAfter another hour
  3. waitso was left
  4. customto react at 50° C. overnight
  5. customAll volatiles were removed under vacuum
  6. dissolutionthe residue dissolved in dichloromethane
  7. additionadded to the 5-bromo-7-azaindole and aluminum trichloride suspension
  8. additionfollowed by the addition of water and extraction with ethyl acetate
  9. dry with materialThe organic layer was dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated
  12. custompurified by silica gel column chromatography
  13. washeluting with a gradient of methanol (0 to 10%) in dichloromethane
  14. customto give the compound (P-1637, 14 mg, 4%)

Sources & evidence

ORD record
ord-0bf6f074ffca4b859e8c0cea3fb0b2c9
Source dataset
uspto-grants-2013_06
Patent number
US08470818B2

Reaction notes

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