1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → benzyl {(5S)-5-{[(5-methoxy-2-methyl-1H-indol-3-yl)acetyl]amino}-5-[5-(2-naphthyl)-1H-imidazol-2-yl]pentyl}carbamate

HRID 659712

Reaction equation

HRID 659712 reaction equation
FC(F)(F)[C:3]([O-:5])=[O:4].F[C:9](F)(F)[C:10]([O-:12])=O.[NH3+:15][C@H:16]([C:32]1[NH:33][C:34]([C:37]2[CH:46]=[CH:45][C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH:38]=2)=[CH:35][NH+:36]=1)[CH2:17][CH2:18][CH2:19][CH2:20][NH:21]C(OCC1C=CC=CC=1)=O.[CH3:47]CN=C=NCCCN(C)C.[CH:58]1[CH:59]=[CH:60][C:61]2N(O)N=N[C:62]=2[CH:63]=1.[CH3:68][O:69][C:70]1[CH:71]=[C:72]2[C:76](=[CH:77][CH:78]=1)[NH:75][C:74]([CH3:79])=[C:73]2CC(O)=O.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:68][O:69][C:70]1[CH:71]=[C:72]2[C:76](=[CH:77][CH:78]=1)[NH:75][C:74]([CH3:79])=[C:73]2[CH2:9][C:10]([NH:15][C@H:16]([C:32]1[NH:33][C:34]([C:37]2[CH:46]=[CH:45][C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH:38]=2)=[CH:35][N:36]=1)[CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:3](=[O:4])[O:5][CH2:47][C:62]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:63]=1)=[O:12]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 761515-Methoxy-2-methylindole-3-acetic acidHCID 81531DiisopropylethylamineHCID 866315362-((1S)-1-ammonio-5-{[(benzyloxy)carbonyl]amino}pentyl)-5-(2-naphthyl)-1H-imidazol-3-ium bis(trifluoroacetate)

Product 1

HCID 86631539benzyl {(5S)-5-{[(5-methoxy-2-methyl-1H-indol-3-yl)acetyl]amino}-5-[5-(2-naphthyl)-1H-imidazol-2-yl]pentyl}carbamateYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution (0.5 M) of the product from step 2 in DMF were added EDCI (1.5 eq.), HOBt (1.5 eq.), (5-methoxy-2-methyl-1H-indol-3-yl)acetic acid (1.5 eq.) and DIPEA (6 eq.) and the reaction mixture was stirred at RT for 16 h. Then, it was diluted with EtOAc and washed with 1N HCl, brine and dried. Evaporation of the solvent under reduced pressure gave a crude that was purified by flash chromatography on silica gel (1:4 to 1:3 EtOAc/petroleum ether) to yield (77%) the title compound as a solid.

Workup

  1. washwashed with 1N HCl, brine
  2. customdried
  3. customEvaporation of the solvent under reduced pressure
  4. customgave a crude that
  5. customwas purified by flash chromatography on silica gel (1:4 to 1:3 EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-a6fd1f79528546ada0afbdf313119303
Source dataset
uspto-grants-2011_12
Patent number
US08080573B2

Linked notes

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