Sodium Bicarbonate → 2-Methyl-5-oxo-4-{3-[3-(trifluoromethyl)phenyl]-1H-indazol-5-yl]-1,4,5,7-tetrahydrofuro[3,4-b]-pyridine-3-carbonitrile

HRID 408559ノート

反応式

HRID 408559 の反応式
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[C:16]([C:17]#[N:18])=[C:15]([CH3:19])[NH:14][C:13]4[CH2:20][O:21][C:22](=[O:23])[C:12]3=4)[CH:9]=2)[NH:4][N:3]=1.[F:24][C:25]([F:36])([F:35])[C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:19][C:15]1[NH:14][C:13]2[CH2:20][O:21][C:22](=[O:23])[C:12]=2[CH:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][N:3]=[C:2]3[C:30]2[CH:29]=[CH:28][CH:27]=[C:26]([C:25]([F:36])([F:35])[F:24])[CH:31]=2)[C:16]=1[C:17]#[N:18]

参加物

6

反応物 3

HCID 516892Sodium BicarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 178428406HCID 178428406、化合物

生成物 1

HCID 469113222-Methyl-5-oxo-4-{3-[3-(trifluoromethyl)phenyl]-1H-indazol-5-yl]-1,4,5,7-tetrahydrofuro[3,4-b]-pyridine-3-carbonitrile収率 4.3%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
95 °C

実験手順

To a degassed solution of 120 mg (0.323 mmol) 4-(3-bromo-1H-indazol-5-yl)-2-methyl-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridine-3-carbonitrile (Example 24) and 73.7 mg (0.388 mmol) [3-(trifluoromethyl)phenyl]boronic acid in anhydrous 1,4-dioxane (4.8 ml) were added under argon atmosphere 37.4 mg (0.032 mmol) tetrakis(triphenylphosphine)palladium(0) and aqueous sodium bicarbonate solution (2 M, 0.77 ml). The resulting mixture was stirred at 95° C. for 12 h. After cooling to room temperature and concentration under reduced pressure, the remaining solid was dissolved in ethyl acetate (20 ml). The solution was subsequently washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (first run: acetonitrile/water gradient, final mixture 95:5 v/v; second run: methanol/water isocratic 75:25 v/v) to yield the title compound as a white solid (6 mg, 4% of th.).

後処理

  1. temperatureAfter cooling to room temperature
  2. concentrationconcentration under reduced pressure
  3. dissolutionthe remaining solid was dissolved in ethyl acetate (20 ml)
  4. washThe solution was subsequently washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative RP-HPLC (first run: acetonitrile/water gradient, final mixture 95:5 v/v; second run: methanol/water isocratic 75:25 v/v)

出典と根拠

ORDレコード
ord-3e0d684fdb974ff28817bb57e24e3baf
出典データセット
uspto-grants-2014_06
特許番号
US08759341B2

反応ノート

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