Pyridine → 4-(bis-methylsulfanyl-methylene)-2-(3-methyl-butyl)-6-thiophen-2-yl-2H-pyridazine-3,5-dione

HRID 421502ノート

反応式

HRID 421502 の反応式
[CH3:1][CH:2]([CH3:18])[CH2:3][CH2:4][N:5]1[C:10](=[O:11])[CH2:9][C:8](=[O:12])[C:7]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)=[N:6]1.F[B-](F)(F)F.[CH3:24][S:25][C:26](=[S+]C)[S:27][CH3:28].O1CCOCC1.N1C=CC=CC=1>C(OCC)(=O)C>[CH3:24][S:25][C:26]([S:27][CH3:28])=[C:9]1[C:8](=[O:12])[C:7]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)=[N:6][N:5]([CH2:4][CH2:3][CH:2]([CH3:18])[CH3:1])[C:10]1=[O:11]

参加物

6

反応物 4

HCID 1049PyridineHCID 312751,4-DioxaneHCID 11021007(Bis-methylsulfanyl-methylene)-methyl-sulfonium tetrafluoroborate saltHCID 574551852-(3-methyl-butyl)-6-thiophen-2-yl-2H-pyridazine-3,5-dione

生成物 1

HCID 580002634-(bis-methylsulfanyl-methylene)-2-(3-methyl-butyl)-6-thiophen-2-yl-2H-pyridazine-3,5-dione収率 20%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

2-(3-Methyl-butyl)-6-thiophen-2-yl-2H-pyridazine-3,5-dione (0.215 g, 0.814 mmol) and (bis-methylsulfanyl-methylene)-methyl-sulfonium tetrafluoro borate salt (prepared as described in WO 2008/011337; 0.79 g, 3.26 mmol) were combined. 1,4-Dioxane (1.06 mL) and pyridine (0.15 mL) were added. The mixture was heated at 100° C. for 1 h while stirring. Upon cooling, the mixture was diluted with ethyl acetate (30 mL) and washed with water (15 mL), saturated aqueous brine solution (15 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was passed through a plug of silica gel (Merck silica gel 60, 40-63 μm; eluting with 25% ethyl acetate in hexanes). Upon concentrating, 4-(bis-methylsulfanyl-methylene)-2-(3-methyl-butyl)-6-thiophen-2-yl-2H-pyridazine-3,5-dione (0.06 g, 0.163 mmol) was obtained as an orange solid. The solid was combined with 2-amino-4-(methanesulfonylamino-methyl)-thiophene-3-sulfonic acid amide (0.07 g, 0.245 mmol). Toluene (5 mL) and 1,4-dioxane (10 mL) were added and the mixture stirred at 100° C. in a sealed vial for 2 h. Upon cooling, the mixture was concentrated in vacuo to afford a thick oil. Purification by flash column chromatography (Teledyne Isco RediSep column; 5-100% ethyl acetate in hexanes) afford the desired product, N-{3-[5-hydroxy-2-(3-methyl-butyl)-3-oxo-6-thiophen-2-yl-2,3-dihydro-pyridazin-4-yl]-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}-methanesulfonamide (0.018 g, 0.032 mmol, 10%) as a light orange powder. 1H NMR (400 MHz, DMSO-d6) δ: 0.95 (6H, d, J=6.2 Hz), 1.57-1.69 (3H, m), 2.97 (3H, s), 4.13 (2H, t, J=7.1 Hz), 4.27 (2H, d, J=5.5 Hz), 7.13-7.16 (1H, m), 7.31 (1H, s), 7.64-7.69 (2H, m), 7.89 (1H, d, J=4.0 Hz). LC-MS (ESI) calculated for C20H23N5O6S4 557.05. found 558.0 [M+H+].

後処理

  1. temperatureUpon cooling
  2. washwashed with water (15 mL), saturated aqueous brine solution (15 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. concentrationUpon concentrating

出典と根拠

ORDレコード
ord-978ba6b3eca84e498674b479e7c5dcca
出典データセット
uspto-grants-2012_01
特許番号
US08097613B2

反応ノート

読み込み中…