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

HRID 855390Notes

Reaction equation

HRID 855390 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:70]=[CH:69][C:53]([CH2:54][NH:55][CH2:56][CH2:57][C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([O:64][C:65]([F:68])([F:67])[F:66])[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:70]=[CH:69][C:53]([CH2:54][N:55]([CH2:56][CH2:57][C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([O:64][C:65]([F:68])([F:67])[F:66])[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 57438500(4-Tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amine

Product 1

HCID 116995785-Chloro-6-fluoro-1H-indole-7-carboxylic acid (4-tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amideYield 25.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 200 mg (0.94 mmol) 5-chloro-6-fluoro-1H-indole-7-carboxylic acid and 300 mg of TBTU (0.94 mmol) in 15 ml DMF, were added 0.8 ml (4.68 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 329 mg (0.94 mmol) (4-tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amine in 1 ml DMF was added. After stirring for 17 h at rt, the reaction mixture was diluted with 160 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 (90 g silica gel; diethylether/heptane 1:1) to give 130 mg off-white foam (23%). MS (ISP) 547.4 (M+H)+.

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 (90 g silica gel; diethylether/heptane 1:1)

Sources & evidence

ORD record
ord-ca06f46fe256414b819ad03f030cec5d
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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