Water → HCID 178422978、化合物

HRID 473165

反応式

HRID 473165 の反応式
[NH2:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[F:12][C:13]([F:24])([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1)[C:14]([O-])=O.[Na+].C[Si](OP(=O)=O)(C)C.O>CCOC(C)=O>[F:24][C:13]([F:12])([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1)[C:14]1[N:6]=[C:4]([OH:5])[C:3]2[C:2](=[CH:10][C:9]([CH3:11])=[CH:8][CH:7]=2)[N:1]=1

参加物

6

反応物 4

HCID 962WaterHCID 28014742-Amino-4-methylbenzamideHCID 16133246Trimethyl(phosphooxy)silaneHCID 66609989Sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate

生成物 1

HCID 178422978HCID 178422978、化合物収率 66.6%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
130 °C

実験手順

To a mixture of 2-amino-4-methylbenzamide (804 mg, 5.36 mmol) and sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate from Example 2 Step B (1.25 g, 5.89 mmol) was added trimethylsilyl polyphosphate (ca. 10 mL) and the mixture was heated at 130° C. in a sand bath overnight. The mixture was allowed to cool to rt, and then water (75 mL) and EtOAc (75 mL) were added and the mixture was stirred at rt for 1 h. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-60% EtOAc/hexanes to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methylquinazolin-4-ol (1.09 g, 66%). LCMS (ESI) m/z 306 (M+H)+.

後処理

  1. temperatureto cool to rt
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 0-60% EtOAc/hexanes

出典と根拠

ORDレコード
ord-1aca565682e64f6b9c259285947cf1cb
出典データセット
uspto-grants-2014_01
特許番号
US08633207B2

関連ノート

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