Toluene → 8-Cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline

HRID 473216ノート

反応式

HRID 473216 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].[CH:24]1(B(O)O)[CH2:26][CH2:25]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl.O>[CH:24]1([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[C:9]([C:12]([F:20])([F:21])[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=2)[N:8]=[C:7]3[S:22][CH3:23])[CH2:26][CH2:25]1

参加物

7

反応物 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 666094698-Bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline

生成物 1

HCID 666098168-Cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline収率 84%

試薬・触媒・溶媒 2

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)触媒HCID 962Water溶媒

反応条件

温度
100 °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 (200 mg, 0.5 mmol), dichlorobis(tricyclohexylphosphine)palladium(II) (37 mg, 0.05 mmol), cyclopropylboronic acid (65 mg, 0.75 mmol) and K3PO4 (371 mg, 1.75 mmol) were added toluene (6 mL) and water (0.5 mL). The reaction vessel was evacuated and flushed with argon (3×), and then the mixture was heated at 100° C. for 4 h. The mixture was concentrated under reduced pressure onto Celite and the residue was purified by silica gel chromatography eluting with 10-50% EtOAc/hexanes to afford impure 8-cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline (150 mg, 84%) which was used without further purification.

後処理

  1. customThe reaction vessel was evacuated
  2. customflushed with argon (3×)
  3. concentrationThe mixture was concentrated under reduced pressure onto Celite
  4. customthe residue was purified by silica gel chromatography
  5. washeluting with 10-50% EtOAc/hexanes

出典と根拠

ORDレコード
ord-4b691892610748fdaab7fcdc1a140446
出典データセット
uspto-grants-2014_01
特許番号
US08633207B2

反応ノート

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