1-Hydroxybenzotriazole → HCID 57584073, compound

HRID 910622Notes

Reaction equation

HRID 910622 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]3[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][CH:23]=3)[C:17]2=[O:31])[CH2:10][CH2:9]1)=O)(C)(C)C.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH2:54][C:55]1[C:70]([OH:71])=[CH:69][CH:68]=[CH:67][C:56]=1[C:57]([NH:59][C:60]1[CH:65]=[CH:64][C:63]([Cl:66])=[CH:62][N:61]=1)=[O:58]>CN(C)C=O.O.C(N(CC)CC)C>[Cl:66][C:63]1[CH:64]=[CH:65][C:60]([NH:59][C:57](=[O:58])[C:56]2[CH:67]=[CH:68][CH:69]=[C:70]([OH:71])[C:55]=2[NH:54][C:26](=[O:28])[C:25]2[CH:24]=[CH:23][C:22]([C:18]3[C:17](=[O:31])[N:16]([CH2:15][CH2:14][N:11]4[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]4)[CH:21]=[CH:20][CH:19]=3)=[CH:30][CH:29]=2)=[N:61][CH:62]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 180011272-amino-N-(5-chloro-2-pyridinyl)-3-hydroxybenzamideHCID 57584146HCID 57584146, compound

Product 1

HCID 57584073HCID 57584073, compoundYield 96.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

4-(1-{2-[4-(tert-butoxycarbonyl)piperazin-1-yl]ethyl}-2-oxo-1,2-dihydropyridin-3-yl)benzoic acid (731 mg) was dissolved in N,N-dimethylformamide (15 mL), 1-hydroxybenzotriazole (253 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (359 mg) and triethylamine (261 μL) were added, and 2-amino-N-(5-chloro-2-pyridinyl)-3-hydroxybenzamide (412 mg) was added, followed by stirring at room temperature for 7 hours. Water was added to the reaction mixture, and the precipitate formed was collected by filtration and washed with water. The resulting solid was dried under reduced pressure and dissolved in tetrahydrofuran (15 mL), and acetic acid (448 μL) was added, followed by stirring at 60° C. for 5 hours. The reaction mixture was concentrated under reduced pressure, and then azeotroped twice with toluene. The residue was purified by NH-silica gel column chromatography (methanol/chloroform=0% to 5%). The resulting compound was dissolved in ethyl acetate (10 mL), and 4 N hydrochloric acid/ethyl acetate (3.88 mL) was added, followed by stirring at room temperature for 20 hours. The reaction mixture was concentrated under reduced pressure, and aqueous saturated sodium hydrogencarbonate solution was added to the residue, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by NH-silica gel column chromatography (methanol/chloroform=0% to 5%) to obtain N-(5-chloropyridin-2-yl)-3-hydroxy-2-({4-[2-oxo-1-(2-piperazin-1-ylethyl)-1,2-dihydropyridin-3-yl]benzoyl}amino)benzamide (867 mg) as a yellow white solid.

Workup

  1. customthe precipitate formed
  2. filtrationwas collected by filtration
  3. washwashed with water
  4. customThe resulting solid was dried under reduced pressure
  5. dissolutiondissolved in tetrahydrofuran (15 mL)
  6. additionacetic acid (448 μL) was added
  7. stirringby stirring at 60° C. for 5 hours
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. customazeotroped twice with toluene
  10. customThe residue was purified by NH-silica gel column chromatography (methanol/chloroform=0% to 5%)
  11. dissolutionThe resulting compound was dissolved in ethyl acetate (10 mL)
  12. addition4 N hydrochloric acid/ethyl acetate (3.88 mL) was added
  13. stirringby stirring at room temperature for 20 hours
  14. concentrationThe reaction mixture was concentrated under reduced pressure, and aqueous saturated sodium hydrogencarbonate solution
  15. additionwas added to the residue
  16. extractionfollowed by extraction with chloroform
  17. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  18. customthe solvent was evaporated under reduced pressure
  19. customthe residue was purified by NH-silica gel column chromatography (methanol/chloroform=0% to 5%)

Sources & evidence

ORD record
ord-3566635431874e97a20161db2a95ea7a
Source dataset
uspto-grants-2011_09
Patent number
US08022208B2

Reaction notes

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