Toluene → HCID 10369153, compound

HRID 620616Notes

Reaction equation

HRID 620616 reaction equation
[CH3:1][CH:2]([N:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[C:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[N:9][CH:8]([NH:23][C:24]([O:26]CC2C=CC=CC=2)=[O:25])[C:7]1=[O:34])[C:3]([OH:5])=O.S(Cl)(Cl)=O.[CH2:39]([NH:41][CH2:42][CH3:43])[CH3:40].[C:44]1([CH3:50])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>>[C:44]1([CH2:50][O:26][C:24](=[O:25])[NH:23][CH:8]2[N:9]=[C:10]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:6]([CH:2]([CH3:1])[C:3]([N:41]([CH2:42][CH3:43])[CH2:39][CH3:40])=[O:5])[C:7]2=[O:34])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

5

Reactant 4

HCID 1140TolueneHCID 8021DiethylamineHCID 24386Thionyl ChlorideHCID 10004266HCID 10004266, compound

Product 1

HCID 10369153HCID 10369153, compound

Conditions

Temperature
90 °C

Procedure

390 mg (0.853 mmol) of 2,3-dihydro-alpha-methyl-2-oxo-5-phenyl-3-((phenylmethoxy)carbonyl)amino-1H-1,4-benzodiazepine-1-acetic acid was suspended in 28 ml toluene, treated with 1.07 ml (14.6 mmol) thionyl chloride, and stirred at 90° C. for 2 hours. The solvent was removed in vacuo and the residue treated with fresh toluene. The cycle was repeated 4 times. The resulting brown oil was dissolved in 5 ml THF, treated with 185 μl (1.79 mmol) of diethylamine and stirred at room temperature for 1 hour. The solvent was removed in vacuo, treated with 10% Na2CO3 solution and extracted (3x EtOAc). The extracts were combined, washed (1x H2O, 1x brine), dried over Na2SO4, filtered and stripped to dryness in vacuo. Flash chromatography of the crude product on silica gel (10% Et2O in CH2Cl2) gave the title compound which was crystallized from Et2O: m.p. 170°-171° C.

Workup

  1. customThe solvent was removed in vacuo
  2. additionthe residue treated with fresh toluene
  3. dissolutionThe resulting brown oil was dissolved in 5 ml THF
  4. stirringstirred at room temperature for 1 hour
  5. customThe solvent was removed in vacuo
  6. additiontreated with 10% Na2CO3 solution
  7. extractionextracted (3x EtOAc)
  8. washwashed (1x H2O, 1x brine)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered

Sources & evidence

ORD record
ord-e5dd91507d8a4b6cb8785e8dad2dbcef
Source dataset
uspto-grants-1989_04
Patent number
US04820834

Reaction notes

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