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Formamide → N-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazolin-8-yl)formamide

HRID 473204
ノート
印刷プレビュー

反応式

HRID 473204 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].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[CH:66]([NH2:68])=[O:67].C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[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]([NH:68][CH:66]=[O:67])[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

7

反応物 4

HCID 713FormamideHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 666094698-Bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline

生成物 1

HCID 86662704N-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazolin-8-yl)formamide収率 74%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °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 (250 mg, 0.63 mmol), tris(dibenzylideneacetone)dipalladium (58 mg, 0.063 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (109 mg, 0.19 mmol), formamide (0.075 mL, 1.875 mmol) and Cs2CO3 (284 mg, 0.875 mmol) was added dioxane (4 mL). The reaction vessel was evacuated and flushed with argon (3×) and the mixture was heated at 90° C. overnight. The mixture was diluted with DCM and concentrated under reduced pressure onto Celite. The residue was purified by silica gel chromatography eluting with 0-50% EtOAc/hexanes to afford N-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazolin-8-yl)formamide (168 mg, 74%).

後処理

  1. customThe reaction vessel was evacuated
  2. customflushed with argon (3×)
  3. additionThe mixture was diluted with DCM
  4. concentrationconcentrated under reduced pressure onto Celite
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with 0-50% EtOAc/hexanes

出典と根拠

ORDレコード
ord-6140300753964b4c84c528ebe34d0a47
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