Toluene → HCID 11979014, compound

HRID 1985545Notes

Reaction equation

HRID 1985545 reaction equation
C([N:4]1[C:12]2[C:7](=[CH:8][C:9]3[CH2:17][C@@H:16]([NH:18][C:19](=O)[O:20]CC4C=CC=CC=4)[C:15](=[O:29])[N:14]([CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH2:13][C:10]=3[CH:11]=2)[CH:6]=[N:5]1)(=O)C.[H][H].[C:39](Cl)(Cl)=[O:40].C1(C)C=CC=CC=1.C([O-])(=O)C.O=C1[N:64]([CH:65]2[CH2:70][CH2:69][NH2+:68][CH2:67][CH2:66]2)[CH2:63][C:62]2[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=2)[NH:56]1.C(=O)([O-])[O-].[K+].[K+]>CO.C(O)(=O)C.[Pd]>[CH2:30]([N:14]1[C:15](=[O:29])[C@H:16]([NH:18][C:19]([N:68]2[CH2:67][CH2:66][CH:65]([N:64]3[CH2:63][C:62]4[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=4)[NH:56][C:39]3=[O:40])[CH2:70][CH2:69]2)=[O:20])[CH2:17][C:9]2[CH:8]=[C:7]3[C:12](=[CH:11][C:10]=2[CH2:13]1)[NH:4][N:5]=[CH:6]3)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

10

Reactant 6

HCID 1140TolueneHCID 6371PhosgeneHCID 11430Potassium CarbonateHCID 59731919HCID 59731919, compoundHCID 67318866HCID 67318866, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 11979014HCID 11979014, compoundYield 11%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

(R)-Benzyl 1-acetyl-8-benzyl-7-oxo-1,5,6,7,8,9-hexahydroazepino[4,3-f]indazol-6-ylcarbamate (52 mg, 0.11 mmol) was dissolved in a mixture of methanol (7 mL) and acetic acid (100 μL). A catalytic amount of 10% palladium on carbon was added to the mixture. Reaction was placed on a Parr apparatus under 60 psi of hydrogen gas. Reaction shook at room temperature for 2 hours. Mixture was filtered. Filtrate was concentrated. Residue was dissolved in dichloromethane (5 mL). Aqueous sodium bicarbonate (5 mL) was added to the mixture. 20% Phosgene in toluene (62 μL, 0.12 mmol) was added to the mixture with vigorous stirring. Reaction was stirred vigorously at room temperature for 20 minutes. 4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)piperidinium acetate was added to the mixture. Reaction stirred at room temperature for 1 hour. Layers were partitioned. Organics were washed twice with 1N hydrochloric acid and once with brine. Organic layer was dried (magnesium sulfate), filtered and concentrated in vacuo. Residue was dissolved in methanol (5 mL). Potassium carbonate (20 mg, 0.14 mmol) was added to the mixture. Reaction stirred at room temperature for 1 hour. Reaction was quenched with trifluoroacetic acid. Mixture was purified by prep HPLC. Title compound was obtained as a white solid in 11% yield. MS m/e (M+H)+=564.3. Rf=1.89 min.

Workup

  1. customReaction
  2. customReaction
  3. filtrationMixture was filtered
  4. concentrationFiltrate was concentrated
  5. dissolutionResidue was dissolved in dichloromethane (5 mL)
  6. additionAqueous sodium bicarbonate (5 mL) was added to the mixture
  7. customReaction
  8. stirringwas stirred vigorously at room temperature for 20 minutes
  9. customReaction
  10. stirringstirred at room temperature for 1 hour
  11. customLayers were partitioned
  12. washOrganics were washed twice with 1N hydrochloric acid and once with brine
  13. dry with materialOrganic layer was dried (magnesium sulfate)
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. dissolutionResidue was dissolved in methanol (5 mL)
  17. customReaction
  18. stirringstirred at room temperature for 1 hour
  19. customReaction
  20. customwas quenched with trifluoroacetic acid
  21. customMixture was purified by prep HPLC

Sources & evidence

ORD record
ord-ce652433cf424aa299c3c2cf12215d2c
Source dataset
uspto-grants-2009_06
Patent number
US07544680B2

Reaction notes

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