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

HRID 855392Notes

Reaction equation

HRID 855392 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:12]([OH:14])=O)[C:10]=1[F:11])[NH:7][CH:6]=[CH:5]2.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:46]([C:50]1[CH:67]=[CH:66][C:53]([CH2:54][NH:55][CH2:56][CH2:57][C:58]2[CH:63]=[CH:62][C:61]([F:64])=[C:60]([Cl:65])[CH:59]=2)=[CH:52][CH:51]=1)([CH3:49])([CH3:48])[CH3:47]>CN(C=O)C.O>[C:46]([C:50]1[CH:67]=[CH:66][C:53]([CH2:54][N:55]([CH2:56][CH2:57][C:58]2[CH:63]=[CH:62][C:61]([F:64])=[C:60]([Cl:65])[CH:59]=2)[C:12]([C:9]2[C:10]([F:11])=[C:2]([Cl:1])[CH:3]=[C:4]3[C:8]=2[NH:7][CH:6]=[CH:5]3)=[O:14])=[CH:52][CH:51]=1)([CH3:49])([CH3:47])[CH3:48]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 251136475-chloro-6-fluoro-1H-indole-7-carboxylic acidHCID 68578391(4-Tert-butyl-benzyl)-[2-(3-chloro-4-fluoro-phenyl)-ethyl]-amine

Product 1

HCID 115771665-Chloro-6-fluoro-1H-indole-7-carboxylic acid (4-tert-butyl-benzyl)-[2-(3-chloro-4-fluoro-phenyl)-ethyl]-amideYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 100 mg (0.47 mmol) 5-chloro-6-fluoro-1H-indole-7-carboxylic acid and 150 mg of TBTU (0.47 mmol) in 7 ml DMF, were added 0.4 ml (2.34 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 150 mg (0.47 mmol) (4-tert-butyl-benzyl)-[2-(3-chloro-4-fluoro-phenyl)-ethyl]-amine in 1 ml DMF was added. After stirring for 17 h at rt, the reaction mixture was diluted with 80 ml water and extracted with EtOAc (2×). 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 (8 g silica gel; diethylether/heptane 1:1; then 8 g silicagel DCM/heptane 70:30 to 90:10) to give 130 mg light yellow foam (52%). MS (EI) 514.1 (M)+.

Workup

  1. stirringAfter stirring for 17 h at rt
  2. extractionextracted with EtOAc (2×)
  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 (8 g silica gel

Sources & evidence

ORD record
ord-5b4205a9b44e4555b916474f9cb5b414
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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