Water → HCID 19700585, compound

HRID 861939Notes

Reaction equation

HRID 861939 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.C(Cl)Cl.CI.[OH-:19].[Na+].[OH2:21]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[CH:3]1[N:1]2[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[CH2:5][N:4]([CH2:5][CH2:6][C:7]([OH:21])=[O:19])[CH2:3][C:2]2=[N:1][CH:2]=1

Participants

7

Reactant 5

HCID 962WaterHCID 6328Methyl iodideHCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 13756818HCID 13756818, compound

Product 1

HCID 19700585HCID 19700585, compound

Reagents, catalysts & solvents 1

HCID 94433Tetrabutylammonium hydrogen sulfateCatalyst

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 (1 gram, 2.36 mmol), methylene chloride (10 mL), water (10 mL), methyl iodide (0.2 mL) and a catalytic amount of tetrabutyl ammonium hydrogen sulphate at room temperature with vigorous stirring was added 1.2 mL of a 2N solution of sodium hydroxide. After 16 hours (overnight) the layers were seperated, the aqueous layer was washed 2×60 mL methylene chloride, and the combined organics were dried over sodium sulfate, decanted, and concentrated in vacuo. The resulting residue, 7-[[4-cyanophenyl]methoxy]-4-propanoic acid, 3,4-dihydro-1,4-benzodiazepine-2-methylmercaptyl-5-one, ethyl ester (1H NMR (CDCl3, δTMS) 7.70 (2H, d, 3JHH =8 Hz, 3,5H:4-NCC6H4), 7.56 (2H, 3JHH =8 Hz, 2,6H:4-NCC6H4), 7.49 (1H, d, 4JHH =3 Hz, C6 ArH), 7.18 (1H, d, 3JHH =9 Hz, C9 ArH), 7.15 (1H, dd, 4JHH =3 Hz, 3JHH =9 Hz, C8 ArH), 5.18 (2H, s, OCH2Ar), 4.16 (2H, q, 3JHH =7 Hz, OCH2), 3.94 (2H, t, 3JHH =7 Hz, NCH2), 3.91 (2H, s, C(S)CH2), 2.78 (2H, t, 3JHH =7 Hz, CH2CO2), 2.52 (3H, s, SMe), 1.24 (3H, t, 3JHH =7 Hz, CH2CH3); MS (FAB) cald. for C23H23N3 O4S 437.1, found MH+ 438.1), was dissolved in dry toluene (15 mL) and allowed to react with 0.23 grams pyridinium hydrogen chloride and 0.64 mL propargyl amine. The reaction was heated to reflux. After 5 hours, the reaction was allowed to cool to room temperature and the reaction concentrated in vacuo. The crude material was purified by column chromatography (SiO2, using ethyl acetate as the eluting solvent, Rf =0.1) to yield 4H-imidazo[1,2-a][1,4]benzodiazepine-5(6H)-propanoic acid, 8-[[4-cyanophenyl]methoxy]-1-methyl-6-oxo, ethyl ester (0.23 grams, 22%). 1H NMR (CDCl3, δTMS) 7.71 (2H, d, 3JHH =8 Hz, 3,5H:4-NCC6H4), 7.56 (2H, 3JHH =8 Hz, 2,6H:4-NCC6H4), 7.53 (1H, d, 4JHH =3 Hz, C6 ArH), 7.24 (1H, d, 3JHH =9 Hz, C9 ArH), 7.18 (1H, dd, 4JHH =3 Hz, 3JHH =9 Hz, C8 ArH), 5.21 (2H, dd, OCH2Ar), 4.52 (1H, d, 2JHH =16 Hz, C5H), 4.30 (1H, d, 2JHH =16 Hz, C5H), 4.16 (2H, q, 3JHH =7 Hz, OCH2), 3.89 (2H, m, NCH2), 2.66 (2H, m, CH2CO2), 2.29 (3H, s, C1-Me), 1.22 (3H, t, 3JHH =7 Hz, CH2CH3).

Workup

  1. customAfter 16 hours (overnight) the layers were seperated
  2. washthe aqueous layer was washed 2×60 mL methylene chloride
  3. dry with materialthe combined organics were dried over sodium sulfate
  4. customdecanted
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting residue, 7-[[4-cyanophenyl]methoxy]-4-propanoic acid, 3,4-dihydro-1,4-benzodiazepine-2-methylmercaptyl-5-one, ethyl ester (1H NMR (CDCl3, δTMS) 7.70 (2H, d, 3JHH =8 Hz, 3,5H:4-NCC6H4), 7.56 (2H, 3JHH =8 Hz, 2,6H:4-NCC6H4), 7.49 (1H, d, 4JHH =3 Hz, C6 ArH), 7.18 (1H, d, 3JHH =9 Hz, C9 ArH), 7.15 (1H, dd, 4JHH =3 Hz, 3JHH =9 Hz, C8 ArH), 5.18 (2H, s, OCH2Ar), 4.16 (2H, q, 3JHH =7 Hz, OCH2), 3.94 (2H, t, 3JHH =7 Hz, NCH2), 3.91 (2H, s, C(S)CH2), 2.78 (2H, t, 3JHH =7 Hz, CH2CO2), 2.52 (3H, s, SMe), 1.24 (3H, t, 3JHH =7 Hz, CH2CH3); MS (FAB) cald. for C23H23N3 O4S 437.1, found MH+ 438.1), was dissolved in dry toluene (15 mL)
  7. customto react with 0.23 grams pyridinium hydrogen chloride and 0.64 mL propargyl amine
  8. temperatureThe reaction was heated to reflux
  9. concentrationthe reaction concentrated in vacuo
  10. customThe crude material was purified by column chromatography (SiO2

Sources & evidence

ORD record
ord-da8fe112c31147c0ab3e4ed9531ed53b
Source dataset
uspto-grants-1998_02
Patent number
US05716951

Reaction notes

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