Diisopropylethylamine → 6-Fluoro-1H-indole-7-carboxylic acid (4-tert-butyl-benzyl)-[2-(3,5-difluoro-phenyl)-ethyl]-amide

HRID 855377Notes

Reaction equation

HRID 855377 reaction equation
[F:1][C:2]1[C:10]([C:11]([OH:13])=O)=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=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:45]([C:49]1[CH:66]=[CH:65][C:52]([CH2:53][NH:54][CH2:55][CH2:56][C:57]2[CH:62]=[C:61]([F:63])[CH:60]=[C:59]([F:64])[CH:58]=2)=[CH:51][CH:50]=1)([CH3:48])([CH3:47])[CH3:46]>CN(C=O)C.O>[C:45]([C:49]1[CH:50]=[CH:51][C:52]([CH2:53][N:54]([CH2:55][CH2:56][C:57]2[CH:58]=[C:59]([F:64])[CH:60]=[C:61]([F:63])[CH:62]=2)[C:11]([C:10]2[C:2]([F:1])=[CH:3][CH:4]=[C:5]3[C:9]=2[NH:8][CH:7]=[CH:6]3)=[O:13])=[CH:65][CH:66]=1)([CH3:48])([CH3:46])[CH3:47]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 117081616-fluoro-1H-indole-7-carboxylic AcidHCID 69342901(4-Tert-butyl-benzyl)-[2-(3,5-difluoro-phenyl)-ethyl]-amine

Product 1

HCID 866030806-Fluoro-1H-indole-7-carboxylic acid (4-tert-butyl-benzyl)-[2-(3,5-difluoro-phenyl)-ethyl]-amideYield 79.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 80 mg (0.45 mmol) of 6-fluoro-1H-indole-7-carboxylic acid and 143 mg of TBTU (0.45 mmol) in 5 ml DMF, were added 0.38 ml (2.23 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 176 mg (0.58 mmol) of (4-tert-butyl-benzyl)-[2-(3,5-difluoro-phenyl)-ethyl]-amine were added. After stirring for 17 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 residue was purified by column chromatography (40 g silica gel; EtOAc/heptane 1:4) to give 166 mg light brown foam (78%). MS 464.1 (M)

Workup

  1. stirringAfter stirring for 17 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 residue was purified by column chromatography (40 g silica gel; EtOAc/heptane 1:4)

Sources & evidence

ORD record
ord-f6bbc6d0d11c4a12ba8943693ce8fced
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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