4-(Bromomethyl)-1,2-difluorobenzene → n-(3,4-Difluoro-benzyl)-n-(6-methoxy-benzo[b]thiophen-2-yl)-pyridin-3-yl-sulfonamide

HRID 57152

反応式

HRID 57152 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:10]=[C:9]([NH:11][S:12]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)(=[O:14])=[O:13])[S:8][C:7]=2[CH:21]=1.CC(C)([O-])C.[K+].[F:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1[F:37])[CH2:32]Br>C1COCC1.CCOC(C)=O>[F:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1[F:37])[CH2:32][N:11]([C:9]1[S:8][C:7]2[CH:21]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=2[CH:10]=1)[S:12]([C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)(=[O:14])=[O:13]

参加物

6

反応物 3

HCID 5814364-(Bromomethyl)-1,2-difluorobenzeneHCID 23665647Potassium tert-butoxideHCID 57920429n-(6-Methoxy-benzo[b]thiophen-2-yl)-pyridin-3-yl-sulfonamide

生成物 1

HCID 57920574n-(3,4-Difluoro-benzyl)-n-(6-methoxy-benzo[b]thiophen-2-yl)-pyridin-3-yl-sulfonamide収率 66%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of compound 141-F (0.488 g; 1.52 mmol) in THF (15 mL) was added 1M potassium tert-butoxide (2.28 mL; 2.28 mmol) and the reaction mixture was stirred at ambient temperature for 30 min. 3,4-Difluorobenzyl bromide (0.409 g; 1.97 mmol), dissolved in THF (1.0 mL), was added drop-wise, and the reaction was stirred at ambient temperature for 18 h. The reaction was diluted with EtOAc, washed with 2N HCl, water, brine, dried over Na2SO4, filtered, the solvent evaporated under reduced pressure. The crude residue was purified by flash column chromatography (SiO2) eluting with a heptane-EtOAc gradient to afford an oily semi-solid, which was further purified by reverse-phase semi-prep HPLC (Gemini, C-18 column; 100×30 mm I.D.; 5μ) eluting with a 55% to 75% MeCN—H2O gradient to afford compound 141-G as a white solid (0.447 g, 66%). 1H-NMR (DMSO-d6): δ 3.76 (s, 3H), 4.89 (s, 2H), 6.93-6.96 (m, 1H), 7.11 (s, 1H), 7.19-7.20 (m, 1H), 7.34-7.43 (m, 3H), 7.60-7.62 (d, 1H), 7.70-7.73 (m, 1H), 8.21-8.24 (m, 1H), 8.93-8.96 (m, 2H); MS: m/z 447.0 (MH+).

後処理

  1. additionwas added drop-wise
  2. stirringthe reaction was stirred at ambient temperature for 18 h
  3. washwashed with 2N HCl, water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe crude residue was purified by flash column chromatography (SiO2)
  8. washeluting with a heptane-EtOAc gradient
  9. customto afford an oily semi-solid, which
  10. customwas further purified by reverse-phase semi-prep HPLC (Gemini, C-18 column; 100×30 mm I.D.; 5μ)
  11. washeluting with a 55% to 75% MeCN—H2O gradient

出典と根拠

ORDレコード
ord-c102e12fb4eb4b879e575d8d4a1cc1c9
出典データセット
uspto-grants-2016_09
特許番号
US09434711B2

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