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Tetraethyltin → 2-(Difluoro(5-fluoropyridin-2-yl)methyl)-8-ethyl-4-(methylthio)quinazoline

HRID 473187
ノート
印刷プレビュー

反応式

HRID 473187 の反応式
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([F:21])([F:20])[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[N:8]=[C:7]2[S:22][CH3:23].[CH2:24]([Sn](CC)(CC)CC)[CH3:25].[Li+].[Cl-]>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.CN(C=O)C>[F:20][C:12]([F:21])([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[C:9]1[N:8]=[C:7]([S:22][CH3:23])[C:6]2[C:11](=[C:2]([CH2:24][CH3:25])[CH:3]=[CH:4][CH:5]=2)[N:10]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 11704TetraethyltinHCID 433294Lithium ChlorideHCID 666094698-Bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline

生成物 1

HCID 666095022-(Difluoro(5-fluoropyridin-2-yl)methyl)-8-ethyl-4-(methylthio)quinazoline収率 73.7%

試薬・触媒・溶媒 2

HCID 178418851HCID 178418851、化合物
触媒
HCID 6228Dimethylformamide溶媒

反応条件

温度
135 °C

実験手順

To a mixture of 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 35 step B (300 mg, 0.75 mmol), bis(tri-tert-butylphosphine)palladium (38 mg, 0.075 mmol), tetraethyltin (0.295 mL, 1.5 mmol), and LiCl (95 mg, 2.25 mmol) was added DMF (15 mL). The reaction vessel was evacuated and flushed with argon (2×). The mixture was then heated in a microwave synthesizer at 135° C. for 30 min. The mixture was partitioned between EtOAc and saturated aq sodium bicarbonate and the organic layer was separated, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure onto Celite. The mixture was purified by silica gel chromatography eluting with 0-10% EtOAc/hexanes to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-ethyl-4-(methylthio)quinazoline (193 mg, 73%) as a white solid. LC-MS (ESI) m/z 350 (M+H)+.

後処理

  1. customThe reaction vessel was evacuated
  2. customflushed with argon (2×)
  3. customThe mixture was partitioned between EtOAc and saturated aq sodium bicarbonate
  4. customthe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure onto Celite
  8. customThe mixture was purified by silica gel chromatography
  9. washeluting with 0-10% EtOAc/hexanes

出典と根拠

ORDレコード
ord-ba75f8f51b434f6fb068a37afaaaf1d6
出典データセット
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08633207B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート