TBAF tetrahydrofuran → HCID 25234232, compound

HRID 2421850Notes

Reaction equation

HRID 2421850 reaction equation
[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([CH:35]=[CH:36][CH:37]=1)[C:6](=[N:8][O:9][C:10]([C:12]1[CH:34]=[CH:33][C:15]2[S:16][CH2:17][CH2:18][N:19]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:14]=2[CH:13]=1)=O)[NH2:7].FC(F)(F)C1C=C(C2N=C(C3C=CC4SCCN(S(C5C=CC(C(F)(F)F)=CC=5)(=O)=O)C=4C=3)ON=2)C=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C1COCC1.CCOC(C)=O.O>[F:38][C:2]([F:1])([F:39])[C:3]1[CH:4]=[C:5]([C:6]2[N:7]=[C:10]([C:12]3[CH:34]=[CH:33][C:15]4[S:16][CH2:17][CH2:18][N:19]([S:20]([C:23]5[CH:24]=[CH:25][C:26]([C:29]([F:30])([F:31])[F:32])=[CH:27][CH:28]=5)(=[O:21])=[O:22])[C:14]=4[CH:13]=3)[O:9][N:8]=2)[CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 2

HCID 11078149TBAF tetrahydrofuranHCID 86628745HCID 86628745, compound

Product 1

HCID 25234232HCID 25234232, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Preparation of 3-(3-(trifluoromethyl)phenyl)-5-(4-(4-(trifluoromethyl)phenylsulfonyl)-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-yl)-1,2,4-oxadiazole 3-(trifluoromethyl)-N′-(4-(4-(trifluoromethyl)phenylsulfonyl)-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carbonyloxy)benzimidamide (38.8 mg, 0.066 mmol) was dissolved in THF (0.5 mL) and 1.0M TBAF/THF (0.5 mL, 0.5 mmol). The reaction was allowed to stir at room temperature for 16 hours. The reaction mixture was diluted with EtOAc (1 mL) and water (1 mL). The layers were separated and the aqueous layer was washed with EtOAc (1 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified by flash column chromatography using a gradient elution of hexanes with 10-60% EtOAc to provide 3-(3-(trifluoromethyl)phenyl)-5-(4-(4-(trifluoromethyl)phenylsulfonyl)-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-yl)-1,2,4-oxadiazole (17.6 mg, 0.031 mmol, 45% yield) as a yellow oil. LCMS (+ESI) m/z=572.05 [M+H]+. The compounds listed in Table 6 were prepared using the procedure outlined in the synthesis of the compound of Example 80. These compounds can be prepared from the appropriate intermediate (selected from Intermediates J to L) by treatment with the appropriate amine under the above-described conditions.

Workup

  1. customThe layers were separated
  2. washthe aqueous layer was washed with EtOAc (1 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by flash column chromatography
  7. washa gradient elution of hexanes with 10-60% EtOAc

Sources & evidence

ORD record
ord-90afe8a2f6fc4615b5a948a87bb23f2c
Source dataset
uspto-grants-2011_06
Patent number
US07960376B2

Reaction notes

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