Ammonia → HCID 21141077, compound

HRID 1657353Notes

Reaction equation

HRID 1657353 reaction equation
[CH2:1]([S:8][CH2:9][C@@H:10]([C:22]([N:24]1[CH2:43][CH2:42][CH2:41][C@H:25]1[C:26]([NH:28][C@H:29]([C:34]([NH:36][CH2:37][C:38]([NH2:40])=[O:39])=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32])=[O:27])=[O:23])[NH:11]C(OCC1C=CC=CC=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N.C(Cl)(Cl)(Cl)Cl.CO>[Pd].C(N(CC)CC)C>[CH2:1]([S:8][CH2:9][C@@H:10]([C:22]([N:24]1[CH2:43][CH2:42][CH2:41][C@H:25]1[C:26]([NH:28][C@H:29]([C:34]([NH:36][CH2:37][C:38]([NH2:40])=[O:39])=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32])=[O:27])=[O:23])[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 19076285HCID 19076285, compoundHCID 68127900HCID 68127900, compound

Product 1

HCID 21141077HCID 21141077, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8471TriethylamineSolvent

Procedure

S-Benzyl-N-benzyloxycarbonyl-L-cysteinyl-L-prolyl-L-leucyl-glycinamide (300 mg.) was dissolved in 35 ml. of anhydrous liquid ammonia and hydrogenated in the presence of freshly prepared palladium black (ca 0.1g.) and triethylamine (0.28 ml.) at the boiling point of the solvent. The reaction was followed by thin layer chromatography (solvent system CCl4 /CH3OH/CH3COOH8:1:1) which showed incomplete reaction (50-60%) after 6 hours. Evaporation of ammonia under nitrogen was followed by addition of methanol (10 ml.) and stirring for 10 min. The catalyst was then removed by filtration and washed with methanol (10 ml.). The combined filtrate and washings were passed through a column (1.2 × 10 cm) of Dowex 50 × 8 (H+ form) which was washed with methanol. The desired material was then eluted with 2N ammonium hydroxide-methanol (1:1) and the eluate evaporated in vacuo. Crystallization from water gave 95.2 mg. (42.3%); m.p. 130°-134°.

Workup

  1. customreaction (50-60%) after 6 hours
  2. customEvaporation of ammonia under nitrogen
  3. additionwas followed by addition of methanol (10 ml.)
  4. customThe catalyst was then removed by filtration
  5. washwashed with methanol (10 ml.)
  6. washwas washed with methanol
  7. washThe desired material was then eluted with 2N ammonium hydroxide-methanol (1:1)
  8. customthe eluate evaporated in vacuo
  9. customCrystallization from water
  10. customgave 95.2 mg

Sources & evidence

ORD record
ord-cbbd0f603afa4efd80baf87445efb04f
Source dataset
uspto-grants-1976_06
Patent number
US03960828

Reaction notes

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