Tetrahydrofuran → 1-Butyl-3-[2-chloro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-urea

HRID 1964921Notes

Reaction equation

HRID 1964921 reaction equation
[CH2:1]([NH:5][C:6](=[O:18])[NH:7][C:8]1[C:9]([Cl:17])=[C:10]([CH:14]=[CH:15][CH:16]=1)[C:11]([OH:13])=O)[CH2:2][CH2:3][CH3:4].S(Cl)(Cl)=O.O1CCCC1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]2[CH:35]=[C:36]3[CH:42]=[CH:41][NH:40][C:37]3=[N:38][CH:39]=2)[CH:29]=1.[Cl-].[Cl-].[Cl-].[Al+3]>CN(C)C=O.ClCCl>[CH2:1]([NH:5][C:6]([NH:7][C:8]1[CH:16]=[CH:15][CH:14]=[C:10]([C:11]([C:42]2[C:36]3[C:37](=[N:38][CH:39]=[C:34]([C:30]4[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=4)[CH:35]=3)[NH:40][CH:41]=2)=[O:13])[C:9]=1[Cl:17])=[O:18])[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 24386Thionyl ChlorideHCID 6451240Aluminum(III) ChlorideHCID 513585515-(Pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridineHCID 580875703-Butyl-ureido-2-chloro-benzoic acid

Product 1

HCID 580862751-Butyl-3-[2-chloro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-ureaYield 26.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To 3-(3-Butyl-ureido)-2-chloro-benzoic acid (587, 103 mg, 0.000380 mol) was added dichloromethane (10 mL, 0.2 mol) followed by thionyl chloride (110 μL, 0.0015 mol) and 1 drop of dimethylformamide to give a suspension. The reaction was stirred at room temperature for 2 hours. Solid material was still present in the reaction mixture, so tetrahydrofuran (0.5 mL, 0.006 mol) was added and continued stirring at room temperature. The reaction became a clear solution after 2 hours, then stirred for another hour. All volatiles were removed under vacuum and the residue stripped from toluene, twice. The solid was then dried under high vacuum for 60 minutes and dissolved in dichloromethane (5 mL). This was added to 5-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine (89, 0.074 g 0.00038 mol, prepared as described in Example 17) which had been treated with aluminum trichloride (0.25 g, 0.0019 mol) in dichloromethane (10 mL) for 1 hour. The reaction was stirred at room temperature overnight, then quenched with methanol (5 mL). The resulting solution was extracted with ethyl acetate and water with added saturated sodium bicarbonate to adjust pH˜8. The organic layer was washed with sodium bicarbonate and brine and dried over magnesium sulfate and filtered. The organic layer was concentrated and purified by silica gel column chromatography eluting with 2% methanol in dichloromethane followed by 5% methanol in dichloromethane to give the compound as a white solid (P-1828, 45 mg, 26%).

Workup

  1. customto give a suspension
  2. additionwas added
  3. stirringcontinued stirring at room temperature
  4. customafter 2 hours
  5. stirringstirred for another hour
  6. customAll volatiles were removed under vacuum
  7. customThe solid was then dried under high vacuum for 60 minutes
  8. dissolutiondissolved in dichloromethane (5 mL)
  9. stirringThe reaction was stirred at room temperature overnight
  10. customquenched with methanol (5 mL)
  11. extractionThe resulting solution was extracted with ethyl acetate and water with added saturated sodium bicarbonate
  12. washThe organic layer was washed with sodium bicarbonate and brine
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationThe organic layer was concentrated
  16. custompurified by silica gel column chromatography
  17. washeluting with 2% methanol in dichloromethane

Sources & evidence

ORD record
ord-2c3f0473108b4531a7dba0c0e7e95d07
Source dataset
uspto-grants-2013_04
Patent number
US08415469B2

Reaction notes

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