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

HRID 1188704Notes

Reaction equation

HRID 1188704 reaction equation
[F:1][C:2]([C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[C:11]([C:14]([F:17])([F:16])[F:15])[C:10]([C:18]#[N:19])=[CH:9][CH:8]=2)([F:4])[CH3:3].C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:27][C:28]1[N:32]=[C:31]([C:33]2[CH:38]=[C:37]([F:39])[CH:36]=[C:35]([F:40])[CH:34]=2)[O:30][N:29]=1.CC#N>CCOC(C)=O>[F:4][C:2]([C:5]1[N:6]([CH2:27][C:28]2[N:32]=[C:31]([C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[C:35]([F:40])[CH:34]=3)[O:30][N:29]=2)[C:7]2[C:12]([CH:13]=1)=[C:11]([C:14]([F:15])([F:17])[F:16])[C:10]([C:18]#[N:19])=[CH:9][CH:8]=2)([F:1])[CH3:3]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 431202093-(Chloromethyl)-5-(3,5-difluorophenyl)-1,2,4-oxadiazoleHCID 674048012-(1,1-difluoroethyl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 866207322-(1,1-Difluoroethyl)-1-{[5-(3,5-difluorophenyl)-1,2,4-oxadiazol-3-yl]methyl}-4-(trifluoromethyl)-1H-indole-5-carbonitrileYield 77.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of the indole (0.050 g, 0.18 mmol) from step A, Cs2CO3 (0.065 g, 0.20 mmol), 3-(chloromethyl)-5-(3,5-difluorophenyl)-1,2,4-oxadiazole (0.046 g, 0.20 mmol) and CH3CN (4 mL) was stirred at 70° C. for 24 h. The mixture was diluted with EtOAc (25 mL), washed with water (15 mL), brine (15 mL), dried over (MgSO4) and concentrated. Added 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 (0.065 g, 76%) as a light tan solid: 1H NMR (400 MHz, DMSO-d6) δ 8.23 (d, J=8.6 Hz, 1H), 7.98 (d, J=8.6 Hz, 1H), 7.74-7.64 (m, 3H), 7.23 (s, 1H), 5.99 (s, 2H), 2.24 (t, 3H); MS m/z 467 (M−H).

Workup

  1. washwashed with water (15 mL), brine (15 mL)
  2. dry with materialdried over (MgSO4)
  3. concentrationconcentrated
  4. additionAdded 10% Et2O in hexanes (10 mL)
  5. stirringstirred for 2 h
  6. filtrationThe resulting solid was filtered
  7. washrinsed with hexanes
  8. customdried

Sources & evidence

ORD record
ord-10eb89e7d9c94856ab6b361af234681a
Source dataset
uspto-grants-2014_03
Patent number
US08673948B2

Reaction notes

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