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

HRID 855382Notes

Reaction equation

HRID 855382 reaction equation
[F: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]([F: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 57438500(4-Tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amineHCID 693460795,6-difluoro-1H-indole-7-carboxylic acid

Product 1

HCID 866030835,6-Difluoro-1H-indole-7-carboxylic acid (4-tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amideYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 50 mg (0.25 mmol) of 5,6-difluoro-1H-indole-7-carboxylic acid and 81 mg of TBTU (0.25 mmol) in 4 ml DMF, were added 0.22 ml (1.28 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 89 mg (0.25 mmol) of (4-tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amine were added. After stirring for 17 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 1:2) to give 56 mg light yellow amorphous material (38%). MS: 530.1 (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; EtOAc/heptane 1:2)

Sources & evidence

ORD record
ord-e456c537450246d285e1b604ef30841a
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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