3-Cyanobenzoic acid → HCID 86652725, compound

HRID 1895910Notes

Reaction equation

HRID 1895910 reaction equation
[F:1][C:2]([F:22])([F:21])[O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[CH2:18][CH2:17][CH:16]([O:19][NH2:20])[CH2:15][CH2:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1.ON1C2C=CC=CC=2N=N1.[C:33]([C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=1)[C:38](O)=[O:39])#[N:34].C(N(CC)C(C)C)(C)C>CN(C)C=O>[C:33]([C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=1)[C:38]([NH:20][O:19][CH:16]1[CH2:17][CH2:18][N:13]([S:10]([C:7]2[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:21])[F:22])=[CH:9][CH:8]=2)(=[O:11])=[O:12])[CH2:14][CH2:15]1)=[O:39])#[N:34]

Participants

6

Reactant 4

HCID 158753-Cyanobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67118448HCID 67118448, compound

Product 1

HCID 86652725HCID 86652725, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(3-Dimethylaminopropyl)-3-ethylcarboiimide hydrochloride (160 mg, 0.84 mmol) was added to a solution of O-(1-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4-yl)hydroxylamine (238 mg, 0.70 mmol), 1-hydroxybenzotriazole (114 mg, 0.84 mmol), 3-cyanobenzoic acid (103 mg, 0.70 mmol) and N,N-diisopropylethylamine (271 mg, 2.10 mmol) in N,N-dimethylformamide (6 ml). The reaction mixture was stirred at room temperature for 17 hours and quenched with H2O (10 ml) and aqueous 1 N HCl solution (pH=3). The aqueous phase was extracted with CH2Cl2 (20 ml×3) and the combined organic phase was washed with aqueous NaHCO3 solution and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/hexane: 33/67) to give 3-cyano-N-(1-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4-yloxy)benzamide (118 mg, 36%) as a white solid: LCMS: 470 [M+1]+. 1H NMR (DMSO-d6) δ: 1.77 (s, 2H), 1.92 (s, 2H), 3.02 (s, 2H), 3.12 (s, 2H), 4.03 (s, 1H), 7.67 (m, 3H), 8.01 (m, 5H), 11.7 (s, 1H).

Workup

  1. customquenched with H2O (10 ml) and aqueous 1 N HCl solution (pH=3)
  2. extractionThe aqueous phase was extracted with CH2Cl2 (20 ml×3)
  3. washthe combined organic phase was washed with aqueous NaHCO3 solution and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (ethyl acetate/hexane: 33/67)

Sources & evidence

ORD record
ord-558bf08a265749bba3ccc085f7f478bc
Source dataset
uspto-grants-2013_08
Patent number
US08518934B2

Reaction notes

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