Hydrochloric Acid → HCID 77780665, compound

HRID 1596380Notes

Reaction equation

HRID 1596380 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.[N:17]1([C:25]([CH2:27][N:28]2[C:34]3[C:35]([CH3:39])=[CH:36][CH:37]=[CH:38][C:33]=3[C:32]([CH:40]=O)=[N:31][CH:30]([NH:42][C:43]([NH:45][C:46]3[CH:51]=[CH:50][CH:49]=[C:48]([CH3:52])[CH:47]=3)=[O:44])[C:29]2=[O:53])=[O:26])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.Cl>O1CCCC1.C(OCC)(=O)C.C1(C)C=CC=CC=1>[N:17]1([C:25]([CH2:27][N:28]2[C:34]3[C:35]([CH3:39])=[CH:36][CH:37]=[CH:38][C:33]=3[C:32]([CH:40]=[CH:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:31][CH:30]([NH:42][C:43]([NH:45][C:46]3[CH:51]=[CH:50][CH:49]=[C:48]([CH3:52])[CH:47]=3)=[O:44])[C:29]2=[O:53])=[O:26])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 21701407HCID 21701407, compound

Product 1

HCID 77780665HCID 77780665, compoundYield 77.8%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of sodium hydride (31 mg, 60% in mineral oil) in tetrahydrofuran was added ethyl diethylphosphonoacetate (195 mg) under stirring and cooling in an ice-bath. After stirring for 15 minutes, a solution 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) in tetrahydrofuran (5 ml) was added to the reaction mixture under the same conditions. The mixture was stirred at ambient temperature for 4 hours. To a reaction mixture was added 0.1N aqueous hydrochloric acid (20 ml) and the resultant mixture was extracted with ethyl acetate. The separated organic layer was washed with water 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 (3:1) to give N-[(3RS)-1-(azacyclooctan-1-yl)carbonylmethyl-2,3-dihydro-5-((EZ)-2-(ethoxycarbonyl)ethenyl)-9-methyl-2-oxo-1H-1,4-benzodiazepin -3-yl]-N′-(3-methylphenyl)urea (266 mg, 77.8% yield) as crystalline powder.

Workup

  1. temperaturecooling in an ice-bath
  2. stirringAfter stirring for 15 minutes
  3. stirringThe mixture was stirred at ambient temperature for 4 hours
  4. extractionthe resultant mixture was extracted with ethyl acetate
  5. washThe separated organic layer was washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was evaporated in vacuo
  8. customto afford a residue, which

Sources & evidence

ORD record
ord-ff4a0727bd464d8ca4bcc3df5cef2335
Source dataset
uspto-grants-2001_09
Patent number
US06291452B1

Reaction notes

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