Dimethylformamide → HCID 24983832, compound

HRID 2101868Notes

Reaction equation

CN(C=O)C.[F:6][C:7]([F:20])([F:19])[C:8]1[C:16]([C:17]#[N:18])=[CH:15][CH:14]=[C:13]2[C:9]=1[CH:10]=[CH:11][NH:12]2.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:28][C:29]1[N:33]=[C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=2)[O:31][N:30]=1>O.CCOC(C)=O>[F:20][C:7]([F:19])([F:6])[C:8]1[C:16]([C:17]#[N:18])=[CH:15][CH:14]=[C:13]2[C:9]=1[CH:10]=[CH:11][N:12]2[CH2:28][C:29]1[N:33]=[C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:41])[F:42])[CH:35]=2)[O:31][N:30]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A DMF solution (25 mL) of 4-(trifluoromethyl)-1H-indole-5-carbonitrile (2.66 mmol max) was treated with Cs2CO3 (1.73 g, 5.32 mmol) followed by 3-(chloromethyl)-5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole (0.699 g, 2.66 mmol). The resulting suspension was heated to 90° C. for 30 min. The cooled reaction mixture was diluted with H2O (25 mL) and then extacted with EtOAc (3×25 mL). The pooled organic portions were washed with H2O and brine. Drying (Na2SO4) and filtration were followed by concentration. Column chromatography (SiO2, EtOAc/hexanes) afforded the title compound in excellent purity as a pale yellow solid (900 g, 75% over two stages): 1H NMR (DMSO-d6) δ 8.32 (d, J=6.0 Hz, 1H), 8.25 (bs, 1H), 8.11-8.06 (m, 2H), 7.98 (d, J=3.0 Hz, 1H), 8.86-8.81 (m, 2H), 6.82-6.81 (m, 1H), 5.95 (s, 2H).

Workup

customThe cooled reaction mixture
washThe pooled organic portions were washed with H2O and brine
customDrying
filtration(Na2SO4) and filtration
concentrationwere followed by concentration

Sources & evidence

ORD record: ord-f3171a3a554249988f2f26a0c75ae8c2
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07572820B2

Reaction notes

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