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

HRID 1011519ノート

反応式

HRID 1011519 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-418c4f33af304a4d813fa9d2bd3e3393
出典データセット
uspto-grants-2011_07
特許番号
US07977362B2

反応ノート

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