Dicyclohexylcarbodiimide → 3-Cyano-6-methoxy-2-[3-(3-methoxycarbonylphenyl)-[1,2,4]oxadiazol-5-yl]-indole-1-carboxylic acid tert-butyl ester

HRID 252540Notes

Reaction equation

HRID 252540 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[C:10]([C:19]#[N:20])=[C:9]1[C:21](O)=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[CH3:49][O:50][C:51](=[O:62])[C:52]1[CH:57]=[CH:56][CH:55]=[C:54]([C:58](=[NH:61])[NH:59]O)[CH:53]=1>ClCCCl.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[C:10]([C:19]#[N:20])=[C:9]1[C:21]1[O:22][N:61]=[C:58]([C:54]2[CH:55]=[CH:56][CH:57]=[C:52]([C:51]([O:50][CH3:49])=[O:62])[CH:53]=2)[N:59]=1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 594261993-Cyano-6-methoxyindole-1,2-dicarboxylic acid 1-tert-butyl esterHCID 178497860HCID 178497860, compound

Product 1

HCID 668660073-Cyano-6-methoxy-2-[3-(3-methoxycarbonylphenyl)-[1,2,4]oxadiazol-5-yl]-indole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 20184825Dce dmfSolvent

Procedure

To a solution of 3-cyano-6-methoxyindole-1,2-dicarboxylic acid 1-tert-butyl ester (474 mg, 1.5 mmol) prepared above, and HOBt (200 mg, 1.5 mmol) in DCE/DMF (10 mL/1 mL), is added DCC (310 mg, 1.5 mmol), followed by 3-(N-hydroxycarbamimidoyl)benzoic acid methyl ester (291 mg, 1.5 mmol). The mixture is stirred at room temperature for 2 h and filtered. The filtrate is collected and the solvent is replaced with chlorobenzene, followed by the heating at 150° C. for 48 h. After cooling to room temperature, the solvent is removed in vacuo and the residue is chromatographed (silica gel, CH2Cl2/EtOAc, 8/2) to furnish the intermediate, 3-cyano-6-methoxy-2-[3-(3-methoxycarbonylphenyl)-[1,2,4]oxadiazol-5-yl]-indole-1-carboxylic acid tert-butyl ester, which is treated with 50% TFA in DCM (10.0 mL) at room temperature for 1 h. After removal of the volatiles in vacuo, the residue is suspended in water and neutralized with K2CO3 to provide the desired product, methyl 3-[5-(3-cyano-6-methoxy-1H-indol-2-yl-)[1,2,4]oxadiazol-3-yl]benzoate, compound 226 (350 mg, 62%).

Workup

  1. filtrationfiltered
  2. customThe filtrate is collected
  3. customheating at 150° C.
  4. customfor 48 h
  5. temperatureAfter cooling to room temperature
  6. customthe solvent is removed in vacuo
  7. customthe residue is chromatographed (silica gel, CH2Cl2/EtOAc, 8/2)

Sources & evidence

ORD record
ord-73316dd6799b4986a78b1108d6b30066
Source dataset
uspto-grants-2011_01
Patent number
US07868037B2

Reaction notes

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