Pinacol → 4-chloro-3-(4-fluoro-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine

HRID 1693728ノート

反応式

HRID 1693728 の反応式
[Cl-].[Li+].C([Mg]Cl)(C)C.Br[C:9]1[C:10]([Cl:33])=[C:11]2[C:17]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[CH:16][N:15]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:12]2=[N:13][CH:14]=1.C(O[B:38]([O:43][CH:44]([CH3:46])[CH3:45])[O:39][CH:40]([CH3:42])[CH3:41])(C)C.OC(C(O)(C)C)(C)C.[Cl-].[NH4+]>C1COCC1.C(OCC)C>[Cl:33][C:10]1[C:9]([B:38]2[O:39][C:40]([CH3:41])([CH3:42])[C:44]([CH3:45])([CH3:46])[O:43]2)=[CH:14][N:13]=[C:12]2[N:15]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:16]=[C:17]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:11]=12

参加物

9

反応物 6

HCID 6425PinacolHCID 21531Triisopropyl borateHCID 25517Ammonium ChlorideHCID 433294Lithium ChlorideHCID 575374765-bromo-4-chloro-3-(4-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418918HCID 178418918、化合物

生成物 1

HCID 575375444-chloro-3-(4-fluoro-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine収率 48.5%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
0 °C

実験手順

580 mg (13.69 mmol) of vacuum dried anhydrous lithium chloride was dissolved in 30 mL of anhydrous THF under nitrogen. The mixture was cooled to 0° C. and 1.5 mL (3.0 mmol) of a 2 M solution of iso-propylmagnesium chloride in anhydrous THF was added. To this mixture was added at 0° C. a solution of 1.064 g (2.33 mmol) of 5-bromo-4-chloro-3-(4-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine in 20 mL of anhydrous THF under nitrogen. The resulting mixture was stirred at 0° C. for 2 h before 1.0 mL (4.3 mmol) of tri-iso-propylborate was added at 0° C. The resulting mixture was allowed to stir at that temperature for 2.5 h. 990 mg (8.38 mmol) of pinacol was added and the mixture stirred for 24 h, allowing to warm to room temperature. The resulting reaction mixture was distributed between diethyl ether and a saturated aqueous solution of ammonium chloride. The organic phase was separated, dried over sodium sulfate and evaporated. The residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate and hexanes to afford 569 mg (1.13 mmol, 48%) of 4-chloro-3-(4-fluoro-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine as a beige solid. 1H-NMR [500 MHz, d6-DMSO] δ: 8.46 (s, 1H), 7.83 (s, 1H), 7.50 (dd (m), 2H), 7.27 (t (m), 2H), 5.68 (s, 2H), 3.57 (t, 2H), 1.32 (s, 12H), −0.09 (s, 9H); MS [MH+] m/z: 503

後処理

  1. additionwas added at 0° C
  2. stirringthe mixture stirred for 24 h
  3. temperatureto warm to room temperature
  4. customThe resulting reaction mixture
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulfate
  7. customevaporated
  8. customThe residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate and hexanes

出典と根拠

ORDレコード
ord-f547480c0ba7405c94b82a736d2dca83
出典データセット
uspto-grants-2012_04
特許番号
US08158647B2

反応ノート

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