Ammonia → HCID 135536776, compound

HRID 1596358Notes

Reaction equation

HRID 1596358 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]([N:16]1C2C=CC=CC=2N=N1)[C:13](O)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[C:31]([C:34]1[CH:40]=[CH:39][CH:38]=[C:37]([CH3:41])[C:35]=1[NH2:36])(=O)[CH3:32].CN1CCOCC1.N>O1CCCC1.CN(C)C=O>[CH2:1]([O:8][C:9]([NH:11][CH:12]1[N:16]=[C:31]([CH3:32])[C:34]2[CH:40]=[CH:39][CH:38]=[C:37]([CH3:41])[C:35]=2[NH:36][C:13]1=[O:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 1796281-(2-Amino-3-methylphenyl)ethan-1-oneHCID 4315963(1H-Benzotriazol-1-yl){[(benzyloxy)carbonyl]amino}acetic acid

Product 1

HCID 135536776HCID 135536776, compoundYield 63.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of N-benzyloxycarbonyl-2-(benzotriazol-1-yl)glycine (14.11 g) in dry tetrahydrofuran (100 ml) were added oxalyl chloride (3.77 ml) and dimethylformamide (3 drops) under stirring at 0° C. in an ice-salt bath under nitrogen stream. After the mixture was stirred under the same conditions for 2 hours, a mixture of 2-acetyl-6-methylaniline (4.30 g) and N-methylmorpholine (8.74 g) in tetrahydrofuran (20 ml) was added dropwise for 20 minutes. After the addition was completed, the mixture was allowed to warm to ambient temperature with stirring. Tetrahydrofuran was removed in vacuo and the residue was dissolved in ethyl acetate. The mixture was washed with water twice and dried over magnesium sulfate. Removal of the solvent gave an intermediate product as an oil, to which was added 20% methanolic ammonia (75 ml) and stirred at ambient temperature overnight. The resultant precipitate was collected by filtration and washed with cold methanol and diisopropyl ether successively, and dried to give (3RS)-3-benzyloxycarbonylamino-5,9-dimethyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one as a white crystalline powder (6.17 g, 63.5%).

Workup

  1. stirringAfter the mixture was stirred under the same conditions for 2 hours
  2. additionwas added dropwise for 20 minutes
  3. additionAfter the addition
  4. temperatureto warm to ambient temperature
  5. stirringwith stirring
  6. customTetrahydrofuran was removed in vacuo
  7. dissolutionthe residue was dissolved in ethyl acetate
  8. washThe mixture was washed with water twice
  9. dry with materialdried over magnesium sulfate
  10. customRemoval of the solvent
  11. customgave an intermediate product as an oil
  12. stirringstirred at ambient temperature overnight
  13. filtrationThe resultant precipitate was collected by filtration
  14. washwashed with cold methanol and diisopropyl ether successively
  15. customdried

Sources & evidence

ORD record
ord-4bc6b39f7a1b41b8aa1ebfd60c6b681d
Source dataset
uspto-grants-2001_09
Patent number
US06291452B1

Reaction notes

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