Boron trifluoride → HCID 58497238, compound

HRID 1254071Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[N:13]([CH3:14])[C:12]([C:15]3[CH:19]=[CH:18][N:17]([CH2:20][CH3:21])[N:16]=3)=[N:11][C:10]=2[C:22]2[CH:27]=[CH:26][C:25]([C:28](=[N:30][OH:31])[NH2:29])=[CH:24][CH:23]=2)=[CH:4][CH:3]=1.[CH:32](OCC)(OCC)OCC.B(F)(F)F>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[N:13]([CH3:14])[C:12]([C:15]3[CH:19]=[CH:18][N:17]([CH2:20][CH3:21])[N:16]=3)=[N:11][C:10]=2[C:22]2[CH:27]=[CH:26][C:25]([C:28]3[N:29]=[CH:32][O:31][N:30]=3)=[CH:24][CH:23]=2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a suspension of step 4 product (250 mg, 0.552 mmol) in triethyl orthoformate (9.09 ml, 55.2 mmol) was added BF3 etherate (0.699 μl, 5.52 μmol) and the mixture stirred at 110° C. for overnight. The reaction mixture was diluted with EtOAc and washed with NaHCO3 (aq), organic layer was dried, and concentrated. The residue was purified on silica gel column eluting a gradient of 8-70% EtOAc in hexane to afford 3-(4-{5-[(4-chlorophenyl)sulfanyl]-2-(1-ethyl-1H-pyrazol-3-yl)-1-methyl-1H-imidazol-4-yl}phenyl)-1,2,4-oxadiazole (130 mg; more polar; the major regioisomer. There was also a minor regioisomer that was the subject of the next example). 1H NMR (500 MHz), [CDCl3]: 8.78 (s, 1H), 8.28 (m, 2H), 8.15 (m, 2H), 7.55 (m, 1H), 7.22 (m, 2H), 7.06 (m, 2H), 6.95 (m, 1H), 4.28 (q, 2H), 4.00 (s, 3H), 1.60 (t, 3H). LCMS: [M+1]+=463.1 (rt=1.16 min). Human FAAH lysate assay: IC50=28.7 nM.

Workup

washwashed with NaHCO3 (aq), organic layer
customwas dried
concentrationconcentrated
customThe residue was purified on silica gel column
washeluting a gradient of 8-70% EtOAc in hexane

Sources & evidence

ORD record: ord-f5bc13165e2843409abcf8500bf6b3be
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08455528B2

Reaction notes

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