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Cesium fluoride → ethyl 8-(4-amino-2,5-difluoro-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate

HRID 1478343
ノート
印刷プレビュー

反応式

HRID 1478343 の反応式
Cl[C:2]1[C:3]([F:22])=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]2=[O:21].[F:23][C:24]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[C:28]([F:40])=[CH:27][C:25]=1[NH2:26].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[NH2:26][C:25]1[C:24]([F:23])=[CH:30][C:29]([C:2]2[C:3]([F:22])=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:15][CH2:14]2)[CH:8]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]3=[O:21])=[C:28]([F:40])[CH:27]=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 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 9927245Ethyl 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylateHCID 579551442,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)aniline

生成物 1

HCID 86696745ethyl 8-(4-amino-2,5-difluoro-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate
収率 75%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6342Acetonitrile溶媒

反応条件

温度
85 °C

実験手順

Ethyl 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (100 mg, 0.32 mmol), 2,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-aniline (667 mg, 2.06 mmol), tricyclohexylphosphine (105 mg, 0.41 mmol) and cesium fluoride (482 mg, 3.2 mmol) were added to ACN (5 mL). The reaction mixture was degassed with argon. Palladium(II) acetate (24 mg, 0.11 mmol) was added. The reaction mixture was heated at 85° C. for 2 h. The reaction mixture was cooled and evaporated in vacuum. Purification by flash silica column chromatography (DCM:MeOH) (1:0 to 9:1) afforded the title compound as a yellow solid (100 mg, 35%).

後処理

  1. customThe reaction mixture was degassed with argon
  2. temperatureThe reaction mixture was cooled
  3. customevaporated in vacuum
  4. customPurification by flash silica column chromatography (DCM:MeOH) (1:0 to 9:1)

出典と根拠

ORDレコード
ord-ab44a33b63cc40bab74ffde5678b426b
出典データセット
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09403818B2

反応ノート

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