Sodium Carbonate → 5-[2-(4-Methoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-trifluoromethyl-pyridin-2-ylamine

HRID 2409566ノート

反応式

HRID 2409566 の反応式
Br[C:2]1[S:6][C:5]2=[N:7][CH:8]=[C:9](I)[N:4]2[N:3]=1.C([C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1)#N.[C:22]([O-:25])([O-])=O.[Na+].[Na+].CC1(C)C(C)(C)OB([C:36]2[CH:37]=[C:38]([C:43]([F:46])([F:45])[F:44])[C:39]([NH2:42])=[N:40][CH:41]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[CH3:22][O:25][C:13]1[CH:14]=[CH:15][C:16]([C:2]2[S:6][C:5]3=[N:7][CH:8]=[C:9]([C:36]4[CH:37]=[C:38]([C:43]([F:46])([F:45])[F:44])[C:39]([NH2:42])=[N:40][CH:41]=4)[N:4]3[N:3]=2)=[CH:17][CH:18]=1

参加物

7

反応物 5

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 468641035-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amineHCID 662215402-Bromo-5-iodoimidazo[2,1-b][1,3,4]thiadiazole

生成物 1

HCID 667170075-[2-(4-Methoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-trifluoromethyl-pyridin-2-ylamine

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

To a mixture of 2-bromo-5-iodoimidazo[2,1-b][1,3,4]thiadiazole (0.150 g, 0.455 mmol), 3-cyanophenylboronic acid (0.477 mmol) and PdCl2(Ph3P)2 (0.064 g) in dioxane (3 mL), an aq. solution of Na2CO3(2 M, 0.9 mL) was added. The reaction mixture was heated at 110° C. for 24 h in a sealed tube. The solvent was evaporated, the residue precipitated with water, and after drying the resulting gum was washed with Et2O. The residue was suspended in dioxane (3 mL), and 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (1.05 eq), PdCl2(Ph3P)2 (0.2 eq) and a sat. solution of K2CO3 (0.9 mL) were added and heated at 100° C. for 16 h. The solvent was evaporated to dryness. The residue was washed with water, followed by ethyl ether. The resulting precipitate was washed with DCM followed by MeOH and purified by preparative HPLC to afford the desired product (0.010 g). HPLC-MS: (5-100% B in 8 min, 0.8 mL/min, 50° C.): tR=5.57 min, [M+H]+ m/z 392.1; 1H NMR (300 MHz, DMSO-d6) δ=8.85 (d, J=1.6 Hz, 1H), 8.36 (d, J=1.9 Hz, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.75 (s, 1H), 7.16 (d, J=8.9 Hz, 2H), 6.72 (s, 2H), 3.86 (s, 3H) ppm.

後処理

  1. customThe solvent was evaporated
  2. customthe residue precipitated with water
  3. customafter drying the resulting gum
  4. washwas washed with Et2O
  5. temperatureheated at 100° C. for 16 h
  6. customThe solvent was evaporated to dryness
  7. washThe residue was washed with water
  8. washThe resulting precipitate was washed with DCM
  9. custompurified by preparative HPLC

出典と根拠

ORDレコード
ord-5bc0ef1f9e5f462881dcf886e4a8dc8c
出典データセット
uspto-grants-2014_08
特許番号
US08815918B2

反応ノート

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