2,6-Lutidine → 1h-Indole-2-carboxylic acid,3-phenyl-1-[[4-(phenylamino)phenyl]methyl]-

HRID 916200Notes

Reaction equation

HRID 916200 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:10]([OH:25])(=[O:24])CCCCCCCCCCCCC.N1C(C)=CC=CC=1C.C(OC(C1NC2C(C=1)=CC=CC=2)=O)C.[NH2:48][C:49]1[CH:70]=[CH:69][C:52]([CH2:53][N:54]2[C:62]3[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=3)[C:56]([C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)=[CH:55]2)=[CH:51][CH:50]=1.O.[OH-].[Li+]>C(OCC)(=O)C.C1COCC1.CO.O.CC([O-])=O.CC([O-])=O.[Cu+2].C1(C)C=CC=CC=1>[NH:48]([C:49]1[CH:50]=[CH:51][C:52]([CH2:53][N:54]2[C:62]3[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=3)[C:56]([C:63]3[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=3)=[C:55]2[C:10]([OH:25])=[O:24])=[CH:69][CH:70]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

10

Reactant 5

HCID 79372,6-LutidineHCID 11005Myristic AcidHCID 66827Phenylboronic AcidHCID 168937Lithium hydroxide, monohydrateHCID 694354711-(4-Amino-benzyl)-3-phenyl-1H-indole indolecarboxylic acid ethyl ester

Product 1

HCID 114642331h-Indole-2-carboxylic acid,3-phenyl-1-[[4-(phenylamino)phenyl]methyl]-

Reagents, catalysts & solvents 4

HCID 8895Cupric acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Phenylboronic acid (0.16 g, 0.81 mmol), Cu(OAc)2 (0.049 g, 0.27 mmol), and myristic acid (0.037 g, 0.16 mmol) were combined in a 100-mL round-bottom flask with a large stir bar. A rubber septum was attached, and dry toluene (2 mL), 2,6-lutidine (0.066 mL, 0.57 mmol), and 1-(4-amino-benzyl)-3-phenyl-1H-indole indolecarboxylic acid ethyl ester (0.20 g, 0.54 mmol) were successively added. The resulting mixture was stirred at a high rate for 24 h, diluted with ethyl acetate (10 mL), filtered through a plug of silica gel, and then purified by column chromatography (5 to 25% EtOAc/hexanes) to give a gummy solid. To a stirred solution of the gummy solid in 15 mL of 2:1:1 THF/MeOH/water was added lithium hydroxide monohydrate (0.1 g, 2.4 mmol). The reaction was stirred at 40° C. for 5 h. Most of the organic solvents was removed and the reaction mixture was made acidic (pH 6) with glacial acetic acid, and the solid was collected and purified by HPLC as a white powder (0.023 g, 10%): 1H NMR (DMSO-d6) δ 5.64 (s, 2H), 6.77 (t, J=7.4 Hz, 1H), 6.96 (d, J=8.5 Hz, 2H), 7.00 (dd, J=7.6, 0.9 Hz, 2H), 7.04(t, J=7.1 Hz, 1H), 7.15-7.19(m, 4H), 7.25 (t, J=7.11 Hz, 1H), 7.39 (t, J=7.4 Hz, 2H), 7.46-7.53 (m, 1H), 7.53 (t, J=7.4 Hz, 2H), 7.54-7.56 (m, 2H), 8.08 (br s, 1H), 13.01 (br s, 1H); MS (ESI) m/z 419 (MH+); MS (ESI) m/z 417 ([M−H]−); HRMS calcd for C28H23N2O2: 419.1757; found (ESI+): 419.1755.

Workup

  1. filtrationfiltered through a plug of silica gel
  2. custompurified by column chromatography (5 to 25% EtOAc/hexanes)
  3. customto give a gummy solid
  4. stirringThe reaction was stirred at 40° C. for 5 h
  5. customMost of the organic solvents was removed
  6. customthe solid was collected
  7. custompurified by HPLC as a white powder (0.023 g, 10%)

Sources & evidence

ORD record
ord-d1a2a13139614f71b308d0ff25e67432
Source dataset
uspto-grants-2007_09
Patent number
US07268159B2

Reaction notes

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