Dimethylformamide → HCID 69735846, compound

HRID 1859838Notes

Reaction equation

HRID 1859838 reaction equation
N1(C(C(O)=O)N[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])C2C=CC=CC=2N=N1.[C:25](Cl)(=[O:29])[C:26](Cl)=O.C[N:32](C=O)C.[NH2:36][C:37]1[CH:42]=[CH:41]C=[CH:39][C:38]=1[C:43](=O)CCC.C[N:49]1[CH2:54][CH2:53]OCC1.[C:55]([O-])(=O)[CH3:56].[NH4+]>C1COCC1>[CH2:15]([O:14][C:12]([CH:26]1[N:36]=[C:37]([CH:38]([CH3:43])[CH3:39])[C:42]2[CH:41]=[CH:55][CH:56]=[CH:53][C:54]=2[N:49]([NH2:32])[C:25]1=[O:29])=[O:13])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 517165Ammonium AcetateHCID 4315963(1H-Benzotriazol-1-yl){[(benzyloxy)carbonyl]amino}acetic acidHCID 12297606HCID 12297606, compound

Product 1

HCID 69735846HCID 69735846, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A slurry of 2-(benzotriazol-1-yl)-N-(benzyloxycarbonyl)glycine (1.1 equiv.; Katritzky, A. R.; Urogdi, L.; Mayence, A. J. Org. Chem. 1990, 55, 2206) in THF (0.3 M) was cooled to 0° C. and treated with oxalyl chloride (1.1 equiv.) in a dropwise manner. To the slurry was added dropwise DMF (0.1 equiv.); stirring was continued at 0° C. for 1 hour. A solution of 1-(2-aminophenyl)-1-butanone and N-methylmorpholine (2.2 equiv.) in THF (1 M in butanone), pre-cooled to 0° C., was added via cannula. Upon completion of the addition, the reaction was warmed to ambient temperature. The mixture was filtered, washing the filter cake with THF. The filtrate was transferred to a three-neck flask and treated with ammonia gas through a dispersion tube for 15 minutes. Methanol (0.3 M in butanone) was added and the ammonia continued to be bubbled through the solution for 1 hour. The reaction was concentrated, diluted with ethyl acetate, and re-concentrated; this was repeated again. The residue was diluted with ethyl acetate and washed twice with 1 N NaOH. The aqueous washes were back-extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated. Acetic acid was added and concentrated in vacuo. The syrup was dissolved in acetic acid (0.6 M in butanone) and treated with ammonium acetate (4.0 equiv.). The reaction was stirred at ambient temperature for 18 hours. The resultant solid was filtered, washing with H2O.

Workup

  1. additionwas added via cannula
  2. additionUpon completion of the addition
  3. filtrationThe mixture was filtered
  4. washwashing the filter cake with THF
  5. customThe filtrate was transferred to a three-neck flask
  6. additiontreated with ammonia gas through a dispersion tube for 15 minutes
  7. additionMethanol (0.3 M in butanone) was added
  8. customto be bubbled through the solution for 1 hour
  9. concentrationThe reaction was concentrated
  10. additiondiluted with ethyl acetate
  11. concentrationre-concentrated
  12. additionThe residue was diluted with ethyl acetate
  13. washwashed twice with 1 N NaOH
  14. extractionThe aqueous washes were back-extracted with ethyl acetate
  15. washThe combined organics were washed with brine
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated
  19. additionAcetic acid was added
  20. concentrationconcentrated in vacuo
  21. dissolutionThe syrup was dissolved in acetic acid (0.6 M in butanone)
  22. stirringThe reaction was stirred at ambient temperature for 18 hours
  23. filtrationThe resultant solid was filtered
  24. washwashing with H2O

Sources & evidence

ORD record
ord-5e1e9d66929f4569a6ddc646e17cdd08
Source dataset
uspto-grants-2003_03
Patent number
US06528505B1

Reaction notes

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