Dicyclohexylcarbodiimide → 13-(S)-[[(9H-Fluoren-9-yl)methoxycarbonyl]amino]-3-(R)-methyl-12-oxo-14-(phenylmethoxy)-6-(phenylmethyl)-2,6,11-triazatetradecanoic acid, 1,1-dimethylethyl ester

HRID 1418623Notes

Reaction equation

HRID 1418623 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:29](O)=[O:30])[CH2:20][O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[NH2:57][CH2:58][CH2:59][CH2:60][CH2:61][N:62]([CH2:75][C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=1)[CH2:63][CH2:64][C@H:65]([NH:67][C:68](=[O:74])[O:69][C:70]([CH3:73])([CH3:72])[CH3:71])[CH3:66]>ClCCl.C(OCC)(=O)C>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@@H:19]([CH2:20][O:21][CH2:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:29](=[O:30])[NH:57][CH2:58][CH2:59][CH2:60][CH2:61][N:62]([CH2:75][C:76]3[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=3)[CH2:63][CH2:64][C@@H:65]([CH3:66])[NH:67][C:68]([O:69][C:70]([CH3:73])([CH3:71])[CH3:72])=[O:74])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 7017914Fmoc-O-benzyl-L-serineHCID 10689168N-[3-[(4-aminobutyl)(phenylmethyl)amino]-1-(R)-methylpropyl]carbamic acid, 1, 1-dimethylethyl ester

Product 1

HCID 8675393313-(S)-[[(9H-Fluoren-9-yl)methoxycarbonyl]amino]-3-(R)-methyl-12-oxo-14-(phenylmethoxy)-6-(phenylmethyl)-2,6,11-triazatetradecanoic acid, 1,1-dimethylethyl esterYield 96.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

1.71 g (4.1.10-3 mol) of N-[(9H-fluoren-9-yl)methoxycarbonyl]-O-phenylmethyl-(L)-serine are dissolved in 60 ml of dichloromethane. The solution is cooled to 0° C. and a solution of 0.55 g (4.10-3 mol) of HOBT and 1.54 g (7.5.10-3 mol) of DCC in 20 ml of dichloromethane is added. The mixture is stirred for 0.5 hour, 1.30 g (3.72.10-3 mol) of N-[3-[(4-aminobutyl)(phenylmethyl)amino]-1-(R)-methylpropyl]carbamic acid, 1, 1-dimethylethyl ester are then added and the reaction mixture is stirred at room temperature for 16 hours. The solvent is removed under reduced pressure and the residue is purified by chromatography on silica gel using an ethyl acetate/methylcyclohexane mixture (1/1 v/v) and then pure ethyl acetate as the eluent to give 2.7 g of the expected product in the form of a white crystalline solid (yield=96%).

Workup

  1. stirringthe reaction mixture is stirred at room temperature for 16 hours
  2. customThe solvent is removed under reduced pressure
  3. customthe residue is purified by chromatography on silica gel using an ethyl acetate/methylcyclohexane mixture (1/1 v/v)

Sources & evidence

ORD record
ord-783bf9f57d18491b950657b284592a9c
Source dataset
uspto-grants-1999_03
Patent number
US05883132

Reaction notes

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