Diisopropylethylamine → 1-{[5-(3,4-Difluorophenyl)-1,2,4-oxadiazol-3-yl]methyl}-2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 1188588Notes

Reaction equation

HRID 1188588 reaction equation
[C:1]([C:3]1[C:4]([C:20]([F:23])([F:22])[F:21])=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13](=[NH:16])[NH:14][OH:15])[C:7]([CH2:17][CH2:18][CH3:19])=[CH:6]2)#[N:2].[F:24][C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][C:33]=1[F:34])[C:28](Cl)=O.C(N(CC)C(C)C)(C)C>C(#N)C>[F:24][C:25]1[CH:26]=[C:27]([C:28]2[O:15][N:14]=[C:13]([CH2:12][N:8]3[C:9]4[C:5](=[C:4]([C:20]([F:22])([F:23])[F:21])[C:3]([C:1]#[N:2])=[CH:11][CH:10]=4)[CH:6]=[C:7]3[CH2:17][CH2:18][CH3:19])[N:16]=2)[CH:31]=[CH:32][C:33]=1[F:34]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27245193,4-Difluorobenzoyl chlorideHCID 178438386HCID 178438386, compound

Product 1

HCID 578001441-{[5-(3,4-Difluorophenyl)-1,2,4-oxadiazol-3-yl]methyl}-2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrileYield 48%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 2-[5-cyano-2-propyl-4-(trifluoromethyl)-1H-indol-1-yl]-N-hydroxyethanimidamide (Example 275A) (0.050 g, 0.154 mmol) in anhydrous acetonitrile (2.0 mL) under N2, was added 3,4-difluorobenzoyl chloride (0.121 g, 0.177 mmol) and N,N-diisopropylethylamine (0.50 mL, 5.21 mmol). The mixture was then heated in a microwave at 150° C. for 30 min. Upon cooling, the mixture was poured onto a biotage prepak column and the mixture was purified by flash chromatography (0-25% EtOAc-hexanes gradient) to give 0.033 g (48% yield) of pure product: MS (ES) m/z 446 (M+).

Workup

  1. temperatureUpon cooling
  2. additionthe mixture was poured onto a biotage prepak column
  3. customthe mixture was purified by flash chromatography (0-25% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-319defce95274a7fbe74306a0a6bf71a
Source dataset
uspto-grants-2014_03
Patent number
US08673948B2

Reaction notes

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