Triethylamine → N-[1-(2-allyl-5'-fluoro-2'-methoxy-biphenyl-4-yl)-ethyl]-3,4-difluoro-benzenesulfonamide

HRID 2422885ノート

反応式

HRID 2422885 の反応式
[CH2:1]([C:4]1[CH:9]=[C:8]([CH:10]([NH2:12])[CH3:11])[CH:7]=[CH:6][C:5]=1[C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[O:20][CH3:21])[CH:2]=[CH2:3].C(N(CC)CC)C.[F:29][C:30]1[CH:31]=[C:32]([S:37](Cl)(=[O:39])=[O:38])[CH:33]=[CH:34][C:35]=1[F:36]>ClCCl>[CH2:1]([C:4]1[CH:9]=[C:8]([CH:10]([NH:12][S:37]([C:32]2[CH:33]=[CH:34][C:35]([F:36])=[C:30]([F:29])[CH:31]=2)(=[O:39])=[O:38])[CH3:11])[CH:7]=[CH:6][C:5]=1[C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[O:20][CH3:21])[CH:2]=[CH2:3]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 27369133,4-Difluorobenzene-1-sulfonyl chlorideHCID 67244664HCID 67244664、化合物

生成物 1

HCID 67245690N-[1-(2-allyl-5'-fluoro-2'-methoxy-biphenyl-4-yl)-ethyl]-3,4-difluoro-benzenesulfonamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of 3′-allyl-4′-hydroxyacetophenone (0.352 g, 2.0 mmol), N-phenyl-bis(trifluoromethane) sulfonimide) (0.710 g, 2.0 mmol) and potassium carbonate (0.830 g, 6.0 mmol) in tetrahydrofuran (3.0 ml) was heated in a microwave oven at 120° C. for 10 min. The resultant mixture was treated with 5-fluoro-2-methoxyphenyl boronic acid (0.680 g, 0.4 mmol), tetrakis(triphenylphosphine)palladium (0) (0.060 g, 0.05 mmol) and dimethylformamide (1.0 ml) and heated in a microwave oven at 120° C. for 10 min. The mixture was partitioned between ethyl acetate and dilute aqueous sodium carbonate solution. The organic phase was dried over anhydrous sodium sulfate, the solvent evaporated and the residue purified by flash chromatography over silica gel eluting with 9:1 heptane/ethyl acetate. Evaporation of solvent under reduced pressure gave 1-(2-allyl-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethanone. A solution of 1-(2-allyl-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethanone (0.319 g, 1.1 mmol), sodium cyanoborohydride (0.140 g, 2.2 mmol) and ammomium acetate (1.7 g, 22 mmol) was stirred under nitrogen at ambient temperature for 72 h, evaporated to dryness under reduced pressure and partitioned between dichloromethane and brine. The organic phase was dried over anhydrous sodium sulfate, the solvent evaporated and the residue purified by flash chromatography over silica gel eluting with 98:2 ethyl acetate/2M ammonia in methanol. Evaporation of solvent under reduced pressure gave 1-(2-allyl-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethylamine. To a solution of 1-(2-allyl-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethylamine (19.0 mg, 0.07 mmol) in dichloromethane (1 ml) was added triethylamine (6.7 mg, 0.07 mmol) and 3,4-di-fluorophenyl sulfonyl chloride (14.2 mg, 0.06 mmol). The solution was stirred overnight and the solvent evaporated. The residue was purified by flash chromatography over silica gel eluting with dichloromethane. Evaporation of solvent under reduced pressure gave the title compound. 1H NMR (400 MHz, CDCl3): δ 7.52-7.42 (m, 2H), 7.13 (q, 1H), 7.04-6.90 (m, 4H), 6.88-6.83 (m, 1H), 6.77 (q, 1H), 5.67 (dt, 1H), 4.99-4.82 (m, 3H), 4.57 (dq, 1H), 3.71 (s, 3H), 3.09 (br s, 2H), 1.51 (d, 3H) ppm; MS (ESI) m/z: value [M+H]+.

後処理

  1. customthe solvent evaporated
  2. customThe residue was purified by flash chromatography over silica gel eluting with dichloromethane
  3. customEvaporation of solvent under reduced pressure

出典と根拠

ORDレコード
ord-d7709572263e487eaae414ea120fdb26
出典データセット
uspto-grants-2011_06
特許番号
US07960365B2

反応ノート

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