Hydrochloric Acid → HCID 131717771, compound

HRID 2082229Notes

Reaction equation

HRID 2082229 reaction equation
[NH:1]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:2]([C:19]([OH:21])=O)[CH2:3][C:4]1[N:8]=[CH:7][N:6]([S:9]([C:12]2[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:5]=1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:45][C@@H:46]([C:59]([NH:61][C@H:62]([C:70]([N:72]([CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1)[CH3:73])=[O:71])[CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)=[O:60])[CH2:47][C:48]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[N:50]([CH:57]=[O:58])[CH:49]=1>CN(C=O)C>[NH:1]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[C@H:2]([C:19]([NH:45][C@@H:46]([C:59]([NH:61][C@H:62]([C:70]([N:72]([CH2:74][C:75]1[CH:76]=[CH:77][CH:78]=[CH:79][CH:80]=1)[CH3:73])=[O:71])[CH2:63][C:64]1[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=1)=[O:60])[CH2:47][C:48]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[N:50]([CH:57]=[O:58])[CH:49]=1)=[O:21])[CH2:3][C:4]1[N:8]=[CH:7][N:6]([S:9]([C:12]2[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=2)(=[O:10])=[O:11])[CH:5]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 6455010Boc-His(Tos)-OHHCID 14999588HCID 14999588, compound

Product 1

HCID 131717771HCID 131717771, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of Boc-His(Tos)-OH (0.82 g) in DMF (10 ml) was cooled at -15° C. To the solution, NMM (0.22 ml) and isobutyl chloroformate (0.26 ml) were added successively and the mixture was stirred for ten minutes. On the other and, a solution of HCl.H-D-Trp(CHO)-Phe-NMeBzl in DMF (10 ml) was cooled at -15° C. and thereto was added NMM (0.22 ml). This solution was added to the above mentioned mixture and stirred for an hour at -15° C. After evaporation and extraction with ethyl acetate, the organic layer was washed successively with 2% hydrochloric acid, water, 2% sodium hydrogencarbonate, water and saturated sodium chloride solution, and dried over magnesium sulfate to give Boc-His(Tos)-D-Trp(CHO)-Phe-NMeBzl. After evaporation, the residue was dissolved in DMF (20 ml). To the solution, pyridinium chloride (2.18 g) was added under stirring at room temperature. After an hour, additional pyridinium chloride (0.5 g) was added and stirred for additional fifty minutes. After evaporation and extraction with ethyl acetate, the organic layer was washed successively with water, 2% hydrochloric acid, water, 2% sodium hydrogencarbonate, water, saturated sodium chloride solution and dried over magnesium sulfate. After evaporation, the residue was subjected to column chromatography on silica gel (60 g) and eluted with a mixture of chloroform and methanol (20:1). The fractions containing the object compound were combined and evaporated. The residue was pulverized with a mixture of ethanol, diethyl ether and n-hexane. The powder was filtered, washed with n-hexane and dried to give Boc-His-D-Trp(CHO)-Phe-NMeBzl (1.04 g).

Workup

  1. additionThis solution was added to the
  2. stirringstirred for an hour at -15° C
  3. customAfter evaporation and extraction with ethyl acetate
  4. washthe organic layer was washed successively with 2% hydrochloric acid, water, 2% sodium hydrogencarbonate, water and saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate

Sources & evidence

ORD record
ord-8805e2a96fb2480f80a539bfbe5a9201
Source dataset
uspto-grants-1993_02
Patent number
US05187156

Reaction notes

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