Water → HCID 19700581, compound

HRID 861941Notes

Reaction equation

HRID 861941 reaction equation
[NH:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[C:5](=O)[NH:4][CH2:3][C:2]1=S.CI.[OH-:16].[Na+].Cl.[NH+]1[CH:24]=[CH:23][CH:22]=CC=1.[C:25]([NH:28][NH2:29])(=O)C.[OH2:30]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[CH:25]1[N:1]2[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[CH2:5][N:4]([CH2:24][CH2:23][C:22]([OH:30])=[O:16])[CH2:3][C:2]2=[N:29][N:28]=1

Participants

9

Reactant 6

HCID 962WaterHCID 6328Methyl iodideHCID 14039AcetohydrazideHCID 14798Sodium HydroxideHCID 13756818HCID 13756818, compoundHCID 21584435Pyridinium hydrochloride

Product 1

HCID 19700581HCID 19700581, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a biphasic solution of 7-[[4-cyanophenyl]methoxy]-4-propanoic acid, 3,4-dihydro-1H-1,4-benzodiazepine-2-thione-5-one, ethyl ester (0.75 grams, 1.77 mmol), prepared as described in part (c) of Example 3, methylene chloride (20 mL), water (20 mL), 0.2 mL methyl iodide, and a catalytic amount of tetrabutyl ammonium hydrogen sulfate was added 1.2 mL 2N sodium hydroxide. After 16 hrs, overnight, of vigorous stirring the layers were seperated. The aqueous layer was washed 3×30 mL methylene chloride and the combined organics were dried over sodium sulfate, decanted, and concentrated in vacuo. the resulting residue was dissolved in toluene (15 mL) and allowed to react with 0.23 grams (2.0 mmol) pyridinium hydrogen chloride and 0.64 grams (8.6 mmol) acetic hydrazide and the reaction was heated to reflux. After 5 hours, the reaction was allowed to cool to room temperature and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, using 5:95 methanol:methylene chloride as the eluting solvent) to yield 0.5 grams (63%) of 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-5(6H)-propanoic acid, 8-[[4-cyanophenyl]methoxy]-1-methyl-6-oxo, ethyl ester. 1H NMR (CDCl3, δTMS) 7.59 (2H, d, 3JHH =8 Hz, 3,5H:4-NCC6H4), 7.46 (2H, 3JHH =8 Hz, 2,6H:4-NCC6H4), 7.45 (1H, d, 4JHH =3 Hz, C6 ArH), 7.17 (1H, d, 3JHH =9 Hz, C9 ArH), 7.12 (1H, dd, 4JHH =3 Hz, 3JHH =9 Hz, C8 ArH), 5.12 (2H, dd, OCH2Ar), 4.61 (1H, d, 2JHH =16 Hz, C5H), 4.25 (1H, d, 2JHH =16 Hz, C5H), 4.01 (2H, q, 3JHH =7 Hz, OCH2), 3.77 (2H, m, NCH2), 2.57 (2H, m, CH2CO2), 2.46 (3H, s, C1-Me), 1.13 (3H, t, 3JHH =7 Hz, CH2CH3); 13C NMR (CDCl3) 171.1, 165.9, 157.6, 152.4, 150.5, 141.0, 132.4, 131.2, 127.5, 124.1, 119.4, 118.3, 116.8, 111.9, 69.3, 60.6, 45.2, 43.3, 32.4, 14.0, 12.1.

Workup

  1. customwere seperated
  2. washThe aqueous layer was washed 3×30 mL methylene chloride
  3. dry with materialthe combined organics were dried over sodium sulfate
  4. customdecanted
  5. concentrationconcentrated in vacuo
  6. dissolutionthe resulting residue was dissolved in toluene (15 mL)
  7. temperaturethe reaction was heated to reflux
  8. waitAfter 5 hours
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by column chromatography (SiO2

Sources & evidence

ORD record
ord-c5896d46118a4d35879bd8a517963f1e
Source dataset
uspto-grants-1998_02
Patent number
US05716951

Reaction notes

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