1-Hydroxybenzotriazole → HCID 68802882, compound

HRID 850892Notes

Reaction equation

HRID 850892 reaction equation
[CH2:1]([O:8][C:9](=[O:68])[C@H:10]([CH2:62][CH:63]1[CH2:67][CH2:66][CH2:65][CH2:64]1)[NH:11]C(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC1C=CC=CC=1C)NC(=O)[C@H](CCC(=O)OC(C)(C)C)NC(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>N1CCCCC1.ClCCl>[CH2:1]([O:8][C:9](=[O:68])[C@H:10]([CH2:62][CH:63]1[CH2:64][CH2:65][CH2:66][CH2:67]1)[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22942137HCID 22942137, compound

Product 1

HCID 68802882HCID 68802882, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8082PiperidineSolvent

Procedure

A solution of 520 mg (0.56 mmol) of N-[N-[N-[O-tert-butyl-N-[(9-fluorenyl)methoxycarbonyl]-L-a-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-3-cyclopentyl-L-alanine benzyl ester in 3 ml of piperidine and 12 ml of dichloromethane was stirred at room temperature for 30 minutes. The solvent was removed by evaporation and the residue was chromatographed on silica gel using firstly ethyl acetate/petrol (1:1) and then methanol/dichloromethane (1:9) for the elution. The resulting amine was added to a solution of 207 mg (0.504 mmol) of N-(9-fluorenyl-methoxycarbonyl)-O-tert-butyl-L-α-aspartic acid, 78 mg (0.51 mmol) of 1-hydroxybenzotriazole and 134 mg (0.7 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 10 ml of dichloromethane and stirred at room temperature for 18 hours. The solution was then extracted with 2M hydrochloric acid and saturated sodium bicarbonate solution and dried over anhydrous magnesium sulphate. Evaporation, trituration with diethyl ether and filtration gave 440 mg of N-[N-[N-[N-O-tert-butyl-N-[(9-fluorenyl)methoxycarbonyl]-L-a-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-3-cyclopentyl-L-alanine benzyl ester as a white solid; MS: m/e 1101 [M+H].

Workup

  1. customThe solvent was removed by evaporation
  2. customthe residue was chromatographed on silica gel using firstly ethyl acetate/petrol (1:1)
  3. washmethanol/dichloromethane (1:9) for the elution
  4. extractionThe solution was then extracted with 2M hydrochloric acid and saturated sodium bicarbonate solution
  5. dry with materialdried over anhydrous magnesium sulphate
  6. customEvaporation, trituration
  7. filtrationwith diethyl ether and filtration

Sources & evidence

ORD record
ord-1c6a913455ad405a8e4bb650e39c2b56
Source dataset
uspto-grants-2000_01
Patent number
US06018020

Reaction notes

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