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

HRID 2101975

Reaction equation

HRID 2101975 reaction equation
[CH2:1]([C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[C:10]([C:13]([F:16])([F:15])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=2)[CH2:2][CH3:3].[F:19][C:20]([F:39])([F:38])[C:21]1[CH:22]=[C:23]([C:31]2[O:35][N:34]=[C:33]([CH2:36]Cl)[N:32]=2)[CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC#N>CCOC(C)=O>[F:39][C:20]([F:19])([F:38])[C:21]1[CH:22]=[C:23]([C:31]2[O:35][N:34]=[C:33]([CH2:36][N:5]3[C:6]4[C:11](=[C:10]([C:13]([F:15])([F:16])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=4)[CH:12]=[C:4]3[CH2:1][CH2:2][CH3:3])[N:32]=2)[CH:24]=[C:25]([C:27]([F:29])([F:28])[F:30])[CH:26]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 27809575-[3,5-Bis(trifluoromethyl)phenyl]-3-(chloromethyl)-1,2,4-oxadiazoleHCID 674051552-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 866206731-({5-[3,5-Bis(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}methyl)-2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrileYield 81%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (0.040 g, 0.16 mmol), 5-[3,5-bis(trifluoromethyl)phenyl]-3-(chloromethyl)-1,2,4-oxadiazole (0.058 g, 0.17 mmol), Cs2CO3 (0.057 g, 0.17 mmol) and CH3CN (4 mL) was stirred at 75° C. for 1.5 h. The mixture was diluted with EtOAc (25 mL), washed with water (15 mL), and brine (15 mL). The organic portion was dried (MgSO4), filtered, and concentrated. The concentrated material was treated with 10% Et2O in hexanes (10 mL) and stirred for 2 h. The resulting solid was filtered, rinsed with hexanes, and dried to afford the title compound (0.070 g, 81%) as a light tan solid: 1H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 2H), 8.50 (s, 1H), 8.03 (d, J=8.6 Hz, 1H), 7.75 (d, J=8.6 Hz, 1H), 6.59 (s, 1H), 5.90 (s, 2H), 2.90 (t, J=7.5 Hz, 2H), 1.79-1.70 (m, 2H), 0.98 (t, J=7.4 Hz, 3H); MS m/z 547 (M+H).

Workup

  1. washwashed with water (15 mL), and brine (15 mL)
  2. dry with materialThe organic portion was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionThe concentrated material was treated with 10% Et2O in hexanes (10 mL)
  6. stirringstirred for 2 h
  7. filtrationThe resulting solid was filtered
  8. washrinsed with hexanes
  9. customdried

Sources & evidence

ORD record
ord-922bcfbb88d4458d81ac02962cd54abd
Source dataset
uspto-grants-2009_08
Patent number
US07572820B2

Linked notes

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