Sodium hydride → Methyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}(2,2,2-trifluoroethyl)carbamate

HRID 626620ノート

反応式

HRID 626620 の反応式
[NH2:1][C:2]1[C:7]([NH:8][C:9](=[O:12])[O:10][CH3:11])=[C:6]([NH2:13])[N:5]=[C:4]([N:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([F:23])[CH:21]=3)[C:16]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])=[N:15]2)[N:3]=1.[H-].[Na+].ClC(Cl)(Cl)S(O[CH2:40][C:41]([F:44])([F:43])[F:42])(=O)=O>C1COCC1.C(OCC)(=O)C>[NH2:1][C:2]1[C:7]([N:8]([CH2:40][C:41]([F:44])([F:43])[F:42])[C:9](=[O:12])[O:10][CH3:11])=[C:6]([NH2:13])[N:5]=[C:4]([N:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([F:23])[CH:21]=3)[C:16]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])=[N:15]2)[N:3]=1

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 900272,2,2-Trifluoroethyl trichloromethanesulphonateHCID 56963347Methyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo [4,3-b]pyridin-1-yl]pyrimidin-5-yl}carbamate

生成物 1

HCID 57335321Methyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}(2,2,2-trifluoroethyl)carbamate

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

Under argon, 142 mg (0.33 mmol) of the compound from example 1 were initially charged in THF (9.5 ml), the mixture was cooled to 0° C. and 13 mg (0.33 mmol) of sodium hydride (60% suspension in mineral oil) were then added. The mixture was stirred at 0° C. for 30 min, and 96 μl (0.67 mmol) of 2,2,2,-trifluoroethyl trichloromethanesulfonate were then added dropwise. The reaction mixture was stirred at RT overnight. The mixture was then diluted with ethyl acetate and the organic phase was washed twice with saturated aqueous sodium bicarbonate solution. The organic phase was dried over magnesium sulfate, filtered and concentrated. The residue was chromatographed on silica gel (mobile phase dichloromethane:methanol 60:1) and the product fractions were concentrated. The crude product obtained in this manner was re-purified by means of preparative RP-HPLC (acetonitrile:water (+0.1% formic acid)−gradient), then suspended in acetonitrile/water and finally dried by lyophilization. This gave 68 mg (40% of theory) of the title compound as a solid.

後処理

  1. stirringThe reaction mixture was stirred at RT overnight
  2. washthe organic phase was washed twice with saturated aqueous sodium bicarbonate solution
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel (mobile phase dichloromethane:methanol 60:1)
  7. concentrationthe product fractions were concentrated

出典と根拠

ORDレコード
ord-575fd3ede042418eb05f03cf24efc97e
出典データセット
uspto-grants-2016_04
特許番号
US09309239B2

反応ノート

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