Isoamyl Nitrite → HCID 178516177, compound

HRID 268456

Reaction equation

HRID 268456 reaction equation
[O:1]=[C:2]1[NH:6][C@H:5]([C:7]([N:9]([C:11](=O)[C@H:12]([CH2:14][C:15]2[N:19]=[CH:18][NH:17]C=2)N)N)=[O:8])[CH2:4][CH2:3]1.N([O:23][CH2:24]CC(C)C)=O.C(N(CC)CC)C.[CH2:36]([O:43][C:44](=[O:57])[C@H:45]([CH2:47][C:48]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[NH:50][CH:49]=1)[NH2:46])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>CN(C)C=O.CS(C)=O.Cl.O1CCCC1>[CH2:36]([O:43][C:44](=[O:57])[C@H:45]([CH2:47][C:48]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[NH:50][CH:49]=1)[NH:46][C:24](=[O:23])[C@H:11]([CH2:12][C:14]1[N:17]=[CH:18][NH:19][CH:15]=1)[NH:9][C:7](=[O:8])[C@@H:5]1[CH2:4][CH2:3][C:2](=[O:1])[NH:6]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

9

Reactant 4

HCID 8053Isoamyl NitriteHCID 8471TriethylamineHCID 7016092L-Tryptophan benzyl esterHCID 178511799HCID 178511799, compound

Product 1

HCID 178516177HCID 178516177, compound

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

N-(5-Oxo-L-prolyl)-L-histidine hydrazide (0.840 g, 3 mmol) is dissolved in a solution at 0°C of dry dimethylformamide (14 ml), dry dimethyl sulfoxide (10.5 ml) and 2.4 N anhydrous gaseous hydrogen chloride in dry tetrahydrofuran (7.5 ml). The solution is cooled to -20°C and isoamyl nitrite (0.57 ml) is added with stirring. The solution is stirred for 30 minutes at -20°C and is then cooled to -24°C. Triethylamine (3.2 ml) is slowly added until the solution is slightly alkaline pH 8-9. While stirring at -20°C, a solution of L-tryptophan benzyl ester (0.970 g, 3.3 mmol) in dry dimethylformamide (3.0 ml) is added. The solution is stirred at -20°C for 30 minutes, at 0°C for 30 minutes, and then at ice bath temperature for 18 hours. The solution is filtered and the precipitate is washed with dry dimethylformamide (2 × 2 ml). The combined filtrates are concentrated under reduced pressure at 40°C. The residue is dissolved in methanol (10 ml), diethyl ether (300 ml) is slowly added, and the precipitate is collected by filtration. The precipitate is once more dissolved in methanol (10 ml) and is precipitated by the addition of diethyl ether (300 ml). The precipitate is crystallized from methanol to give the title compound as a fine white powder, m.p. 250°-252°C, [α]D25 +1.6° (c = 1.0, DMF).

Workup

  1. stirringThe solution is stirred for 30 minutes at -20°C
  2. temperatureis then cooled to -24°C
  3. stirringWhile stirring at -20°C
  4. stirringThe solution is stirred at -20°C for 30 minutes, at 0°C for 30 minutes
  5. filtrationThe solution is filtered
  6. washthe precipitate is washed with dry dimethylformamide (2 × 2 ml)
  7. concentrationThe combined filtrates are concentrated under reduced pressure at 40°C
  8. dissolutionThe residue is dissolved in methanol (10 ml)
  9. additiondiethyl ether (300 ml) is slowly added
  10. filtrationthe precipitate is collected by filtration
  11. dissolutionThe precipitate is once more dissolved in methanol (10 ml)
  12. customis precipitated by the addition of diethyl ether (300 ml)
  13. customThe precipitate is crystallized from methanol

Sources & evidence

ORD record
ord-c72b20e087264ec4a2246852a9432918
Source dataset
uspto-grants-1976_03
Patent number
US03947569

Linked notes

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