Diisopropylethylamine → [Rac]-5,6-difluoro-1h-indole-7-carboxylic acid (4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-2-hydroxy-ethyl]-amide

HRID 855386Notes

Reaction equation

HRID 855386 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:67]=[CH:66][C:53]([CH2:54][NH:55][CH2:56][CH:57]([C:59]2[CH:64]=[CH:63][C:62]([F:65])=[CH:61][CH:60]=2)[OH:58])=[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][CH:57]([C:59]2[CH:60]=[CH:61][C:62]([F:65])=[CH:63][CH:64]=2)[OH:58])[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 69342608[Rac]-(4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-2-hydroxy-ethyl]-amineHCID 693460795,6-difluoro-1H-indole-7-carboxylic acid

Product 1

HCID 69365967[Rac]-5,6-difluoro-1h-indole-7-carboxylic acid (4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-2-hydroxy-ethyl]-amideYield 47%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 43 mg (0.22 mmol) of 5,6-difluoro-1H-indole-7-carboxylic acid and 68 mg of TBTU (0.22 mmol) in 2 ml DMF, were added 0.19 ml (1.09 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 66 mg (0.22 mmol) of [rac]-(4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-2-hydroxy-ethyl]-amine were added. After stirring for 17 h at rt, the reaction mixture was diluted with 20 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 foam (47%). MS(ISP): 481.4 (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 (8 g silica gel; EtOAc/heptane 1:2)

Sources & evidence

ORD record
ord-cddcb732129847bab5c2346ff9934eab
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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