1H-Indole-7-carboxylic acid → 1H-Indole-7-carboxylic acid (4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide

HRID 855345

Reaction equation

HRID 855345 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([OH:12])=O)[CH:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[C:44]([C:48]1[CH:64]=[CH:63][C:51]([CH2:52][NH:53][CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([F:62])=[CH:58][CH:57]=2)=[CH:50][CH:49]=1)([CH3:47])([CH3:46])[CH3:45]>CN(C=O)C.O>[C:44]([C:48]1[CH:64]=[CH:63][C:51]([CH2:52][N:53]([CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([F:62])=[CH:58][CH:57]=2)[C:10]([C:8]2[CH:7]=[CH:6][CH:5]=[C:4]3[C:9]=2[NH:1][CH:2]=[CH:3]3)=[O:12])=[CH:50][CH:49]=1)([CH3:47])([CH3:45])[CH3:46]

Participants

7

Reactant 4

HCID 742811H-Indole-7-carboxylic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 29280418(4-Tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amine

Product 1

HCID 866030491H-Indole-7-carboxylic acid (4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amideYield 83.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 48 mg (0.3 mmol) of 1H-indole-7-carboxylic acid and 96 mg of TBTU (0.3 mmol) in 4 ml DMF, were added 0.26 ml (1.5 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 86 mg (0.3 mmol) of (4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amine in 1 ml DMF were added. After stirring for 4 h at rt, the reaction mixture was diluted with 50 ml water and extracted with 2×50 ml EtOAc. The combined organic phases were washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The orange residue was purified by column chromatography (8 g silica gel; heptane/EtOAc 6:1) to give 107 mg (82%) of a white solid. MS (ISP) 429.6 (M+H)+.

Workup

  1. stirringAfter stirring for 4 h at rt
  2. extractionextracted with 2×50 ml EtOAc
  3. washThe combined organic phases were washed with water and brine
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe orange residue was purified by column chromatography (8 g silica gel; heptane/EtOAc 6:1)

Sources & evidence

ORD record
ord-7ad5a2dac9994671a1d518d3180ca0d6
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Linked notes

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