Acetic Anhydride → HCID 21701345, compound

HRID 1596381Notes

Reaction equation

HRID 1596381 reaction equation
[N:1]1([C:9]([CH2:11][N:12]2[C:18]3[C:19]([CH3:23])=[CH:20][CH:21]=[CH:22][C:17]=3[C:16]([CH:24]=O)=[N:15][CH:14]([NH:26][C:27]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[CH:31]=3)=[O:28])[C:13]2=[O:37])=[O:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH2:39]O.C([O-])(=O)C.[Na+].C(OC(=O)C)(=O)C.C(=O)([O-])O.[Na+]>C(O)(=O)C.C(OCC)(=O)C.C1(C)C=CC=CC=1>[N:1]1([C:9]([CH2:11][N:12]2[C:18]3[C:19]([CH3:23])=[CH:20][CH:21]=[CH:22][C:17]=3[C:16]([C:24]#[N:39])=[N:15][CH:14]([NH:26][C:27]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[CH:31]=3)=[O:28])[C:13]2=[O:37])=[O:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

9

Reactant 5

HCID 7918Acetic AnhydrideHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 21701407HCID 21701407, compound

Product 1

HCID 21701345HCID 21701345, compoundYield 27.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of N-[(3RS)-1-(Azacyclooctan-1-yl)carbonylmethyl-2,3-dihydro-5-formyl-9-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-N′-(3-methylphenyl)urea (300 mg), hydroxylamine hydrochloride (41 mg) and sodium acetate (51 mg) in acetic acid (1.5 ml) was stirred at ambient temperature for 2.5 hours. Acetic anhydride (0.4 ml) was added to the reaction mixture, and the resultant mixture was stirred at 90° C. for 11.5 hours. After the reaction mixture was allowed to cool to ambient temperature, ethyl acetate and aqueous sodium hydrogen carbonate were added into the mixture successively under stirring. The separated organic layer was washed with aqueous sodium hydrogen carbonate and brine, and dried over magnesium sulfate. The solvent was evaporated in vacuo to afford a residue, which was subjected to column chromatography on silica gel eluting with a mixture of toluene and ethyl acetate (4:1) to give N-[(3RS)-1-(azacyclooctan-1-yl)carbonylmethyl-5-cyano-2,3-dihydro-9-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-N′-(3-methylphenyl)urea as crystalline powder (80 mg).

Workup

  1. temperatureto cool to ambient temperature
  2. stirringunder stirring
  3. washThe separated organic layer was washed with aqueous sodium hydrogen carbonate and brine
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was evaporated in vacuo
  6. customto afford a residue, which

Sources & evidence

ORD record
ord-bc2301fb95e34b0c96c5460932a238b2
Source dataset
uspto-grants-2001_09
Patent number
US06291452B1

Reaction notes

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