Cesium fluoride → (E)-methyl 6-amino-2-(4-chloro-2,3-difluorophenyl)-5-(2-(trimethylsilyl)vinyl)pyrimidine-4-carboxylate

HRID 244309

反応式

HRID 244309 の反応式
[CH3:1][Si:2]([CH3:15])([CH3:14])/[CH:3]=[CH:4]/B1OC(C)(C)C(C)(C)O1.[NH2:16][C:17]1[N:22]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([F:30])[C:24]=2[F:31])[N:20]=[C:19]([C:32]([O:34][CH3:35])=[O:33])[C:18]=1Br.[F-].[Cs+].P(C1C=C(S([O-])(=O)=O)C=CC=1)(C1C=C(S([O-])(=O)=O)C=CC=1)C1C=C(S([O-])(=O)=O)C=CC=1.[Na+].[Na+].[Na+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[NH2:16][C:17]1[N:22]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([F:30])[C:24]=2[F:31])[N:20]=[C:19]([C:32]([O:34][CH3:35])=[O:33])[C:18]=1/[CH:4]=[CH:3]/[Si:2]([CH3:1])([CH3:14])[CH3:15]

参加物

8

反応物 4

HCID 25953Cesium fluorideHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 149278394,4,5,5-Tetramethyl-2-((1E)-2-(trimethylsilyl)ethenyl)-1,3,2-dioxaborolaneHCID 70497348Methyl 6-amino-5-bromo-2-(4-chloro-2,3-difluorophenyl)pyrimidine-4-carboxylate

生成物 1

HCID 70497076(E)-methyl 6-amino-2-(4-chloro-2,3-difluorophenyl)-5-(2-(trimethylsilyl)vinyl)pyrimidine-4-carboxylate収率 43%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒2 回HCID 6342Acetonitrile溶媒

反応条件

温度
150 °C

実験手順

(E)-Trimethyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)silane (470 mg, 2.1 mmol, 1.2 equiv) and methyl 6-amino-5-bromo-2-(4-chloro-2,3-difluorophenyl)pyrimidine-4-carboxylate (650 mg, 1.7 mmol, 1.0 equiv) were sequentially added to a 5 mL Biotage microwave vessel, followed by cesium fluoride (260 mg, 1.7 mmol, 1.0 equiv), palladium(II) acetate (19 mg, 0.086 mmol, 0.05 equiv), and sodium 3,3′,3″-phosphinetriyltribenzenesulfonate (98 mg, 0.17 mmol, 0.10 equiv). A 3:1 mixture of water:acetonitrile (3.5 mL) was added and the resulting brown mixture was placed in a Biotage microwave and heated to 150° C. for 15 m. The cooled reaction mixture was diluted with water (150 mL) and extracted with dichloromethane (3×50 mL). The combined organic layers were dried (magnesium sulfate), gravity filtered, and concentrated under vacuum. The product was purified by silica gel column chromatography (17% ethyl acetate in hexane) to afford the title compound as an off-white powder (290 mg, 43% yield): mp 139-141° C.; 1H NMR (300 MHz, CDCl3) δ 7.76 (m, 1H), 7.22 (m, 1H), 6.94 (d, 1H, J=20 Hz), 6.37 (d, 1H, J=20 Hz), 5.38 (br s, 2H), 3.92 (s, 3H), 0.19 (s, 9H); IR (neat film) 3449 (m), 3350 (s), 3242 (m), 3103 (w), 2954 (m), 1728 (s), 1634 (s); ESIMS m/z 398 ([M+H]+).

後処理

  1. customThe cooled reaction mixture
  2. extractionextracted with dichloromethane (3×50 mL)
  3. dry with materialThe combined organic layers were dried (magnesium sulfate), gravity
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe product was purified by silica gel column chromatography (17% ethyl acetate in hexane)

出典と根拠

ORDレコード
ord-84589f7714fd45aaaceaed02f83f0202
出典データセット
uspto-grants-2014_02
特許番号
US08658568B2

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