4-Methylmorpholine → HCID 13891106, compound

HRID 345909Notes

Reaction equation

[NH:1]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C@H:2]([C:9](O)=[O:10])[CH2:3][C:4]1N=CN[CH:5]=1.ON1[C:24]2[CH:25]=CC=[CH:28][C:23]=2N=N1.CN1CCO[CH2:32][CH2:31]1.CN(C)CCCN=C=NCC.C([O-])(O)=O.[Na+]>Cl>[C:15]([O:14][C:12]([NH:1][C@@H:2]([CH2:3][CH:4]1[CH2:5][CH2:25][CH2:24][CH2:23][CH2:28]1)[CH:9]([OH:10])[CH:31]=[CH2:32])=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

Conditions

Temperature: -23 °C

Procedure

The resultant compound from Example 13g (2.23 g, 4.87 mmol) was stirred for 1 h in 4.5M ethanolic HCl (15 ml). The solvent was evaporated with ether and toluene chasers and the residue was dissolved in dimethylformamide (25 ml) and treated with Boc-His-OH (1.37 g, 5.36 mmol) and 1-hydroxybenzotriazole (1.98 g, 14.6 mmol). The mixture was cooled to -23° C. and N-methylmorpholine (600 microliters, 5.46 mmol) was added followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.05 g, 5.46 mmol). The mixture was stirred at -23° C. for 2 h and at room temperature 16 h, and then was poured into saturated NaHCO3 solution and extracted into ethyl acetate which was washed with water and brine, then dried over Na2SO4 and evaporated. Chromatography of the residue on silica gel with 4% methanol in chloroform provided 1.785 g (72%) of the desired product as a white solid. 1H-NMR (CDCl3, TMS) delta 7.58 (s,1H), 6.89 (s,1H), 6.26 (m,1H), 4.39 (m,1H), 4.13 (m, 1H), 4.40 (m,1H), 3.30 (m,2H), 3.16 (dd,1H , 3.01 (dd,1H), 1.47 (s,9H), 1.17 (t,3H).

Workup

customThe solvent was evaporated with ether and toluene chasers
dissolutionthe residue was dissolved in dimethylformamide (25 ml)
extractionextracted into ethyl acetate which
washwas washed with water and brine
dry with materialdried over Na2SO4
customevaporated

Sources & evidence

ORD record: ord-af43ff06abac4316bf48fb1e7f7d7031
Source dataset: uspto-grants-1991_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05059589

Reaction notes

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