Triethylamine → 4-chloro-N-(2,5-difluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide

HRID 1011519Notes

Reaction equation

HRID 1011519 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:20][C:21]2[CH:26]=[C:25]([F:27])[C:24]([C:28]#[N:29])=[CH:23][C:22]=2[F:30])[C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[CH2:18][OH:19])(=[O:10])=[O:9])=[CH:4][CH:3]=1.Cl.N[OH:33].C([N:36]([CH2:39]C)CC)C>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]([CH2:20][C:21]2[CH:26]=[C:25]([F:27])[C:24]([C:28]3[N:36]=[CH:39][O:33][N:29]=3)=[CH:23][C:22]=2[F:30])[C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[CH2:18][OH:19])(=[O:10])=[O:9])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 594977814-chloro-N-(4-cyano-2,5-difluorobenzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide

Product 1

HCID 468980974-chloro-N-(2,5-difluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamideYield 46%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 4-chloro-N-(4-cyano-2,5-difluorobenzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (198 mg, 0.44 mmol), hydroxylamine hydrochloride (153 mg, 2.2 mmol), and triethylamine (300 uL, 2.2 mmol) was refluxed in 5 mL ethanol for 3 h. The reaction was concentrated and the residue was partitioned between ethyl acetate and sat, sodium bicarbonate solution. The organic layer was dried over magnesium sulfate and concentrated. The crude intermediate was stirred in 3 mL triethylorthoformate with two drops of boron trifluoride etherate at room temperature overnight. The reaction was purified by preparative HPLC followed by flash chromatography on silica gel with 0 to 60% ethyl acetate in hexane to yield 4-chloro-N-(2,5-difluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (100 mg, 46%). 1H NMR (400 MHz, CDCl3) δ ppm 8.81 (s, 1H), 7.69-7.82 (m, 3H), 7.58 (dd, J=10.20, 5.92 Hz, 1H), 7.50 (d, J=8.56 Hz, 2H), 4.49-4.58 (m, 1H), 4.35-4.45 (m, 1H), 3.62-3.73 (m, 2H), 3.08-3.19 (m, 1H), 2.54 (br. s., 1H), 1.60-1.76 (m, 3H), 1.38-1.49 (m, 2H), 0.99-1.24 (m, 4H). Analytical HPLC R.T.=22.87 min. MS [M+H]+=498; [M+Na]+=520. HRMS [M+H]+ calc'd 498.1066, found 498.1063.

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue was partitioned between ethyl acetate
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe reaction was purified by preparative HPLC

Sources & evidence

ORD record
ord-418c4f33af304a4d813fa9d2bd3e3393
Source dataset
uspto-grants-2011_07
Patent number
US07977362B2

Reaction notes

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