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

HRID 855379Notes

Reaction equation

HRID 855379 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([OH:13])=O)[CH:10]=1)[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:45]([C:49]1[CH:69]=[CH:68][C:52]([CH2:53][NH:54][CH2:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[C:59]([O:63][C:64]([F:67])([F:66])[F:65])[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:69]=[CH:68][C:52]([CH2:53][N:54]([CH2:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[C:59]([O:63][C:64]([F:67])([F:66])[F:65])[CH:58]=2)[C:11]([C:9]2[CH:10]=[C:2]([Cl:1])[CH:3]=[C:4]3[C:8]=2[NH:7][CH:6]=[CH:5]3)=[O:13])=[CH:51][CH:50]=1)([CH3:48])([CH3:46])[CH3:47]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57438500(4-Tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amineHCID 668685635-chloro-1H-indole-7-carboxylic acid

Product 1

HCID 116350965-Chloro-1H-indole-7-carboxylic acid (4-tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amideYield 77.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 50 mg (0.26 mmol) of 5-chloro-1H-indole-7-carboxylic acid and 82 mg of TBTU (0.26 mmol) in 4 ml DMF, were added 0.22 ml (1.28 mmol) of N,N-diisopropyl-ethyl amine. After stirring for 5 min at rt, 101 mg (0.33 mmol) of (4-tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amine were added. After stirring for 4 h at rt, the reaction mixture was diluted with 40 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; EtOAc/heptane 1:4) to give 106 mg light brown foam (43%). MS (ISP) 529.4 (M+H)+.

Workup

  1. stirringAfter stirring for 4 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; EtOAc/heptane 1:4)

Sources & evidence

ORD record
ord-d45fdc66be0947a78b09f7b4c22a6b80
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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