Reaction #219169

ord-4c8cbafb971d410e8d145e2866d1e668

Reaction equation

Cn1ccc2ccccc21
N-methyl indole
CS(=O)(=O)O.O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
P2O5 MeSO3H
[N].c1ccc2[nH]ccc2c1
indole nitrogen
CI
MeI
c1ccc2[nH]ccc2c1
esters
c1ccc2[nH]ccc2c1
indole
O=C([O-])[O-].[K+].[K+]
K2CO3
→
O=C1CCNC(=O)c2[nH]ccc21
aldisine

Reactants

Cn1ccc2ccccc21
N-methyl indole
CS(=O)(=O)O.O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
P2O5 MeSO3H
[N].c1ccc2[nH]ccc2c1
indole nitrogen
CI
MeI
c1ccc2[nH]ccc2c1
esters
c1ccc2[nH]ccc2c1
indole
O=C([O-])[O-].[K+].[K+]
K2CO3

Reagents

None

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Otherwas used for the synthesis of 3

Procedure

Starting with the commercially available 2-indolecarboxylic acid, condensation with the ethyl ester of β-alanine in the presence of EDCI and DMAP, provided the indole 4. Methylation of the indole nitrogen with MeI and K2CO3 proceeded in near quantitative yields, rendering the N-methyl indole, which was used for the synthesis of 3. Hydrolysis of esters 4 and 5 followed by the P2O5/MeSO3H mediated cyclization provided the key intermediate aldisine derivatives 8 and 9.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07385055B2uspto-grants-2008_06