Hydrogen Sulfide → Acetate

HRID 861940Notes

Reaction equation

HRID 861940 reaction equation
[CH:1]1[N:5]2[C:6]3[CH:19]=[CH:18][CH:17]=[CH:16][C:7]=3[CH2:8][N:9]([CH2:11][CH2:12][C:13]([OH:15])=[O:14])[CH2:10][C:4]2=[N:3][CH:2]=1.C(N(CC)CC)C.S.[OH-].[Na+]>N1C=CC=CC=1.CO>[CH:1]1[N:5]2[C:6]3[CH:19]=[CH:18][CH:17]=[CH:16][C:7]=3[CH2:8][N:9]([CH2:11][CH2:12][C:13]([OH:15])=[O:14])[CH2:10][C:4]2=[N:3][CH:2]=1.[C:13]([O-:15])(=[O:14])[CH3:12]

Participants

8

Reactant 4

HCID 402Hydrogen SulfideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 19700585HCID 19700585, compound

Product 2

HCID 175AcetateYield 5%HCID 19700585HCID 19700585, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4H-imidazo[1,2-a][1,4]benzodiazepine-5(6H)-propanoic acid, 8-[[4-cyanophenyl]methoxy]-1-methyl-6-oxo, ethyl ester (0.1 grams, 0.22 mmol), in 2 mL pyridine and 2 mL triethylamine was added hydrogen sulfide gas via a pipette to saturation and the reaction stirred for 20 mins. A stream of nitrogen was passed over the reaction mixture for 20 mins., The mixture was concentrated in vacuo, diluted with methylene chloride (2 mL) and allowed to react with methyl iodide (2 mL). The mixture was heated briefly to 50° C., shirred for 30 mins., concentrated in vacuo, diluted with methanol and the reaction allowed to react with ammonium acetate (0.25 grams). Again the reaction was heated briefly to 50° C. and stirred for an additional 30 mins. The mixture was concentrated in vacuo and purified by HPLC (solvent gradient 1:4 acetonitrile:water(0.5% acetic acid) (time 0 to 10 mins.) to 3:2 acetonitrile:water(0.5% acetic acid) (time 50). The major component isolated by HPLC was diluted in methanol (2 mL) and allowed to react 2N sodium hydroxide (2 mL). After 15 mins. the mixture was quenched with glacial acetic acid (0.5 mL) and purified by HPLC (same eluting conditions as those described above) to yield 4H-imidazo[1,2-a][1,4]benzodiazepine-5(6H)-propanoic acid, 8-[[4-(aminoiminomethyl)phenyl]methoxy]-1-methyl-6-oxo, acetate (0.005 grams, 5%). 1H NMR (D2O, δHOD) 7.63 (2H, d, 3 JHH =8 Hz, 3,5H:4-NCC6H4), 7.53 (2H, 3JHH =8 Hz, 2,6H:4-NCC6H4), 7.44 (1H, d, 3JHH =9 Hz, C6 ArH), 7.36 (1H, d, 4JHH =3 Hz, C9 ArH), 7.26 (1H, dd, 4 JHH =3 Hz, 3JHH =9 Hz, C8 ArH), 7.17 (1H, bq, C2H), 5.21 (2H, dd, OCH2Ar), 3.78 (1H, d, 2JHH=16 Hz, C4H), 3.79 (1H, dt, NCHH), 3.63 (1H, dr, NCHH), 2.54 (2H, m, CH2CO2), 2.22 (3H, s, C1-Me). Exact mass (FAB, MH+) cald for C23H24N5 O4 : 434.1828, found 434.1794.

Workup

  1. waitA stream of nitrogen was passed over the reaction mixture for 20 mins
  2. concentration, The mixture was concentrated in vacuo
  3. additiondiluted with methylene chloride (2 mL)
  4. customto react with methyl iodide (2 mL)
  5. waitshirred for 30 mins
  6. concentration, concentrated in vacuo
  7. additiondiluted with methanol
  8. customto react with ammonium acetate (0.25 grams)
  9. temperatureAgain the reaction was heated briefly to 50° C.
  10. stirringstirred for an additional 30 mins
  11. concentrationThe mixture was concentrated in vacuo
  12. custompurified by HPLC (solvent gradient 1:4 acetonitrile
  13. customwater(0.5% acetic acid) (time 0 to 10 mins.)
  14. customThe major component isolated by HPLC
  15. waitAfter 15 mins
  16. customthe mixture was quenched with glacial acetic acid (0.5 mL)
  17. custompurified by HPLC (
  18. washsame eluting conditions as

Sources & evidence

ORD record
ord-4720f397200a4c978ffd616eb19b4e34
Source dataset
uspto-grants-1998_02
Patent number
US05716951

Reaction notes

Loading…