Ethylmorpholine → HCID 178501408, compound

HRID 1855748Notes

Reaction equation

HRID 1855748 reaction equation
[N:1]1([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=O.ON1C2C=CC=CC=2N=N1.[NH2:29][C@H:30]([C:37]([O:39][CH3:40])=[O:38])[CH2:31][C:32]1[N:36]=[CH:35][NH:34][CH:33]=1.Cl.Cl.C(N1CCOCC1)C>CN(C)C=O>[CH2:12]([O:11][C:9]([N:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([NH:29][C@H:30]([C:37]([O:39][CH3:40])=[O:38])[CH2:31][C:32]1[N:36]=[CH:35][NH:34][CH:33]=1)=[O:5])=[O:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 101987Benzyloxycarbonyl-L-prolineHCID 178419105HCID 178419105, compound

Product 1

HCID 178501408HCID 178501408, compoundYield 67.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of N,N1 -dicyclohexylcarbodiimide (DCC, 13.6 g, 66 mmol) in distilled dimethylformamide (DMF, 15 ml) is added dropwise to a cold solution (0° to 5° C.) of Z-Pro-OH (15 g, 60 mmol) and 1-hydroxybenzotriazole (HOBt, 12.16 g, 120 mmol), in distilled DMF (40 ml). The mixture is stirred at 0°-5° C. for 2 hr. Thereafter, a solution of H-His-OMe.2HCl (14.56 g, 60 mmol) and N-ethylmorpholine (15.2 g, 16.89 ml, 132 mmol) in distilled DMF is added to the cold reaction mixture. The pH of the reaction mixture is adjusted to 8 and the reaction mixture stirred for 18 hr at 20°-22° C. The solid (N,N1 -dicyclohexylurea) is removed from the mixture by filtration. The filtrate is concentrated to dryness under reduced pressure. The residue is subjected to chromatography on silica gel (2400 g) using chloroform-methanolpyridine (89:10:1) as the eluant. The pure fractions are pooled and evaporated under reduced pressure to give 16.2 g of the title compound; NMR (CDCl3) δ 3.70 (s, 3H), 5.12 (s, 2H), 7.25 (s, 5H); amino acid analysis: His (1.00), Pro (0.97).

Workup

  1. stirringthe reaction mixture stirred for 18 hr at 20°-22° C
  2. customThe solid (N,N1 -dicyclohexylurea) is removed from the mixture by filtration
  3. concentrationThe filtrate is concentrated to dryness under reduced pressure
  4. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-f2d767a24e9e424fb9245f64e0a42da5
Source dataset
uspto-grants-1980_08
Patent number
US04216209

Reaction notes

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