Cesium carbonate → Methyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-fluorobenzoate

HRID 515219

反応式

HRID 515219 の反応式
Br[C:2]1[CH:19]=[CH:18][C:5]2[N:6]([CH2:12][CH:13]3[CH2:15][C:14]3([F:17])[F:16])[S:7](=[O:11])(=[O:10])[N:8]([CH3:9])[C:4]=2[CH:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([O:29][CH3:30])=[O:28])=[CH:23][C:22]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.CCOC(C)=O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:16][C:14]1([F:17])[CH2:15][CH:13]1[CH2:12][N:6]1[C:5]2[CH:18]=[CH:19][C:2]([C:22]3[CH:23]=[C:24]([CH:25]=[CH:26][C:21]=3[F:20])[C:27]([O:29][CH3:30])=[O:28])=[CH:3][C:4]=2[N:8]([CH3:9])[S:7]1(=[O:11])=[O:10]

参加物

8

反応物 3

HCID 10796Cesium carbonateHCID 230053662-Fluoro-5-(methoxycarbonyl)benzeneboronic acidHCID 682450025-Bromo-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

生成物 1

HCID 67411528Methyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-fluorobenzoate

試薬・触媒・溶媒 4

HCID 178418851HCID 178418851、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

5-bromo-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (4-1) (100 mg, 0.28 mmol, 1 eq), [2-fluoro-5-(methoxycarbonyl)phenyl]boronic acid (84 mg, 0.43 mmol, 1.5 eq), cesium carbonate (185 mg, 0.57 mmol, 2.0 eq) and bis(tri-t-butylphosphine)palladium(0) (29 mg, 0.06 mmol, 0.2 eq) were combined in dioxane (1.5 mL) and water (0.3 mL). The resulting mixture was heated in the microwave at 100° C. for 10 minutes. The reaction mixture was diluted with EtOAc (10 mL), washed with water (2 mL) and brine (2 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (12 g SiO2, 0-70% EtOAc in hexanes) to afford methyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-fluorobenzoate (17-1) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.14 (dd, J=1.6, 6.0 Hz, 1 H); 8.01 (m, 1 H); 7.21 (m, 2 H); 6.95 (t, J=1.2 Hz, 1 H); 6.90 (d, J=6.4 Hz, 1 H); 3.94 (s, 3 H); 3.91 (d, J=5.6 Hz, 2 H); 3.33 (s, 3 H); 2.14 (m, 1 H); 1.64 (m, 1 H); 1.39 (m, 1 H).

後処理

  1. washwashed with water (2 mL) and brine (2 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by flash chromatography (12 g SiO2, 0-70% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-fd38925c2cb943349b06e77c1c30b641
出典データセット
uspto-grants-2015_08
特許番号
US09108937B2

関連ノート

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