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

HRID 1011529노트

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HRID 1011529 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

HCID 468980974-chloro-N-(2,5-difluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide수율 71.7%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

A mixture of 4-chloro-N-(4-cyano-2,5-difluorobenzyl)-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (320 mg, 0.70 mmol) (Example 25), hydroxylamine hydrochloride (247 mg, 3.5 mmol), and triethylamine (488 uL, 3.5 mmol) was refluxed in 8 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 5 mL triethylorthoformate with three drops of boron trifluoride etherate at room temperature overnight. The reaction was purified 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-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (250 mg, 71%). 1H NMR (400 MHz, CDCl3) δ ppm 8.81 (s, 1H), 7.70-7.79 (m, 3H), 7.58 (dd, J=10.20, 5.92 Hz, 1H), 7.50 (d, J=8.56 Hz, 2H), 4.54 (d, J=15.60 Hz, 1H), 4.41 (d, J=15.60 Hz, 1H), 3.64 (td, J=7.93, 3.78 Hz, 2H), 3.14 (t, J=10.58 Hz, 1H), 2.52 (br. s., 1H), 1.58-1.74 (m, 3H), 1.45-1.53 (m, 2H), 1.02-1.26 (m, 4H). Analytical HPLC R.T.=22.92 min. MS [M+H]+=498. HRMS [M+H] calc'd 498.1066, found 498.1087. Chiral LC: R.T.=9.84 min., 99% ee. Optical rotation: [α]=−36.66°, CHCl3 (c=4.29 mg/mL).

후처리

  1. concentrationThe reaction was concentrated
  2. customthe residue was partitioned between ethyl acetate and sat. sodium bicarbonate solution
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe reaction was purified by flash chromatography on silica gel with 0 to 60% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-7d15dfc2fcc742aa9a8a92158109d188
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07977362B2

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