1-Hydroxybenzotriazole → HCID 178427523, compound

HRID 1976618Notes

Reaction equation

HRID 1976618 reaction equation
[NH:1]([C:44](OCC1C=CC=CC=1)=[O:45])[C@@H:2]([C:20]([NH:22][C@H:23]([C:31]([N:33]([CH3:43])[CH2:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[O:32])[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:21])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10].[NH:54]([C:71]([O:73][CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1)=[O:72])[C@H:55](C(O)=O)[CH2:56][C:57]1[CH:62]=[CH:61][C:60]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[CH:59][CH:58]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CO.[Pd]>[NH:54]([C:71]([O:73][CH2:74][C:75]1[CH:76]=[CH:77][CH:78]=[CH:79][CH:80]=1)=[O:72])[C@H:55]([C:44]([NH:1][C@@H:2]([C:20]([NH:22][C@H:23]([C:31]([N:33]([CH3:43])[CH2:34][CH2:35][C:36]([O:38][C:39]([CH3:40])([CH3:42])[CH3:41])=[O:37])=[O:32])[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:21])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:13]=[CH:14][C:15]([CH3:16])=[CH:17][CH:18]=1)(=[O:11])=[O:10])=[O:45])[CH2:56][C:57]1[CH:58]=[CH:59][C:60]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[CH:61][CH:62]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 978520O-(1,1-Dimethylethyl)-N-((phenylmethoxy)carbonyl)-L-tyrosineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178427576HCID 178427576, compound

Product 1

HCID 178427523HCID 178427523, compoundYield 77.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
-10 °C

Procedure

Z-D-Arg(Tos)-Phe-MeβAla-O-t-Bu (31.9 g, 41.0 mmol) was dissolved in methanol (200 ml), and added with 5% Pd-C (water content: 50%, 32 g) as catalyst, and catalytic reduction was carried out for four hours to remove the protective group. After the catalyst was removed by filtration, the solvent was evaporated under reduced pressure, and then the residue was dissolved in dimethylformamide (100 ml). Z-Tyr(t-Bu)-OH (13.7 g, 36.9 mmol) and 1-hydroxybenzotriazole (5.54 g, 41.0 mmol) were dissolved in the solution. This solution was cooled to −10° C., added with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (7.86 g, 41.0 mmol), and then stirred at −10° C. for one hour and further at room temperature for 20 hours. After the solvent was evaporated under reduced pressure, the reaction mixture was added with ethyl acetate (100 ml), and washed with 1N hydrochloric acid and then with saturated aqueous sodium hydrogencarbonate. The solvent was concentrated under reduced pressure to obtain an oily product, which was purified by silica gel column chromatography (chloroform: methanol=40:1 (v/v)) to obtain 27.8 g of Z-Tyr(t-Bu)-DArg(Tos)-Phe-MeβAla-O-t-Bu as white powder.

Workup

  1. customto remove the protective group
  2. customAfter the catalyst was removed by filtration
  3. customthe solvent was evaporated under reduced pressure
  4. dissolutionthe residue was dissolved in dimethylformamide (100 ml)
  5. customAfter the solvent was evaporated under reduced pressure
  6. additionthe reaction mixture was added with ethyl acetate (100 ml)
  7. washwashed with 1N hydrochloric acid
  8. concentrationThe solvent was concentrated under reduced pressure
  9. customto obtain an oily product, which
  10. customwas purified by silica gel column chromatography (chloroform: methanol=40:1 (v/v))

Sources & evidence

ORD record
ord-cb32733454e242e08d21ba6c5cfe98ea
Source dataset
uspto-grants-2001_05
Patent number
US06228841B1

Reaction notes

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