Dimethylformamide → HCID 10227990, compound

HRID 431707Notes

Reaction equation

HRID 431707 reaction equation
[CH3:1][N:2]1[C:6]([C:7]([NH:9][C:10]2[CH:11]=[C:12]([C:16](NCCC(N)=N)=[O:17])[N:13]([CH3:15])[CH:14]=2)=[O:8])=[CH:5][C:4]([NH:24][C:25]([CH2:27]NC(N)=N)=[O:26])=[CH:3]1.[NH2:32][C:33]1[CH:38]=[C:37](O)[CH:36]=[CH:35][C:34]=1[CH2:40][CH2:41][Cl:42].CCN=C=NC[CH2:49][CH2:50]N(C)C.CN(C=[O:58])C>>[Cl:42][CH2:41][CH2:40][C:34]1[CH:35]=[C:36]([OH:58])[CH:37]=[CH:38][C:33]=1[NH:32][C:16]([C:12]1[N:13]([CH3:15])[CH:14]=[C:10]([NH:9][C:7]([C:6]2[N:2]([CH3:1])[CH:3]=[C:4]([NH:24][C:25](=[O:26])[CH2:27][CH2:49][CH3:50])[CH:5]=2)=[O:8])[CH:11]=1)=[O:17]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 18761430HCID 18761430, compoundHCID 178481052HCID 178481052, compound

Product 1

HCID 10227990HCID 10227990, compoundYield 6%

Procedure

In the preparation of the achiral seco-compounds that contain netropsin moieties, 2-(2-amino-4-hydroxyphenyl)ethyl chloride was reacted at 0-50° C., preferably at room temperature, with N-methyl-4-(N-methyl-4-butanamidopyrrole-2-carboxamide)-pyrrole-2-carboxylic acid in the presence of EDCI in DMF to give the desired compound N-(2-(2-chloroethyl)-4-hydroxyphenyl)-1-methyl-4-(1-methyl-4-butanamidopyrrole-2-carboxamido)pyrrole-2-carboxamide in 6% yield, after silica gel column purification. Similarly, coupling of 2-(2-amino-4-hydroxyphenyl)ethyl bromide with N-methyl-4-(N-methyl-4-butanamidopyrrole-2-carboxamide)-pyrrole-2-carboxylic acid gave N-(2-(2-bromoethyl)-4-hydroxyphenyl)-1-methyl-4-(1-methyl-4-butanamidopyrrole-2-carboxamido)pyrrole-2-carboxamide in 40% yield. Subsequent reaction of N-(2-(2-bromoethyl)-4-hydroxyphenyl)-1-methyl-4-(1-methyl-4-butanamido-pyrrole-2-carboxamido)pyrrole-2-carboxamide at 0-50° C., preferably at 5° C., with 4-nitrobenzyl chloroformate in the presence of triethylamine gave the prodrug N-[2-(2-bromoethyl)-O-(4-nitrobenzylcarbonato)phenyl]-1-methyl-4-(1-methyl-4-butanamidopyrrole-2-carboxamido)pyrrole-2-carboxamide in 12% yield.

Workup

  1. customIn the preparation of the achiral seco-compounds that

Sources & evidence

ORD record
ord-56dda5f9218a48e28ac22b4ad6267c23
Source dataset
uspto-grants-2003_12
Patent number
US06660742B2

Reaction notes

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