Ethylmorpholine → HCID 86741771, compound

HRID 2308804Notes

Reaction equation

HRID 2308804 reaction equation
[CH:1]1([C:6]([NH:8][C@H:9]([C:22]([NH:24][C@H:25]([C:32](O)=[O:33])[CH2:26][C:27]2[S:28][CH:29]=[CH:30][CH:31]=2)=[O:23])[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[SH:47][CH2:48][CH2:49][C:50]([NH:52][C:53]([CH3:58])([CH3:57])[C:54]([OH:56])=[O:55])=[O:51].C(N1CCOCC1)C>CN(C)C=O>[CH:1]1([C:6]([NH:8][C@H:9]([C:22]([NH:24][C@H:25]([C:32]([S:47][CH2:48][CH2:49][C:50]([NH:52][C:53]([CH3:58])([CH3:57])[C:54]([OH:56])=[O:55])=[O:51])=[O:33])[CH2:26][C:27]2[S:28][CH:29]=[CH:30][CH:31]=2)=[O:23])[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 7525EthylmorpholineHCID 682631,1'-CarbonyldiimidazoleHCID 12805576HCID 12805576, compoundHCID 22838202HCID 22838202, compound

Product 1

HCID 86741771HCID 86741771, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
-10 °C

Procedure

A solution of 10 mmoles of Nα -cyclopentanecarbonyl-Nε -tert-butyloxycarbonyl-L-lysyl-β-2-thienyl-alanine in redistilled dimethylformamide (DMF) is cooled in an ice-dry ice-acetone bath at -20° C. To this solution is added a cold solution of 10 mmoles of 1,1'-carbonyldiimidazole in DMF. The solution is stirred at -10° C. for two hours and then mixed with a cold solution of 10 mmoles of 2-[(3-mercaptopropanoyl)amino]-2-methylpropanoic acid (from Example 46) in DMF which is neutralized with N-ethyl morpholine. The reaction mixture is stirred at -10° C. for an additional hour and then slowly warmed to room temperature. The solvent is removed under reduced pressure at 40° C. and ethyl acetate is added to the residue. The mixture is cooled in an ice water bath and washed with 1N citric acid and then three times with saturated NaCl solution. The solvent is removed with a rotary evaporator after drying over anhydrous MgSO4. The product is purified by LH-20 column chromatography using a 1.2 cm by 95 cm column and eluted with THF:isopropanol, 3:7 (parts by volume). The peak fractions are pooled and the solvent is removed under reduced pressure yielding the named product.

Workup

  1. stirringThe reaction mixture is stirred at -10° C. for an additional hour
  2. temperatureslowly warmed to room temperature
  3. customThe solvent is removed under reduced pressure at 40° C.
  4. additionethyl acetate is added to the residue
  5. temperatureThe mixture is cooled in an ice water bath
  6. washwashed with 1N citric acid
  7. customThe solvent is removed with a rotary evaporator
  8. dry with materialafter drying over anhydrous MgSO4
  9. customThe product is purified by LH-20 column chromatography
  10. washeluted with THF
  11. customthe solvent is removed under reduced pressure
  12. customyielding the named product

Sources & evidence

ORD record
ord-2ce4df360e6c47f889e9e5ece803bc4f
Source dataset
uspto-grants-1987_09
Patent number
US04690936

Reaction notes

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