Acetonitrile → Methyl 6-amino-2-(2,5-difluoro-4-(trimethylsilyl)phenyl)-5-methoxypyrimidine-4-carboxylate

HRID 516556

反応式

HRID 516556 の反応式
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[C:5]([F:17])=[CH:4][C:3]=1[Si:18]([CH3:21])([CH3:20])[CH3:19].[NH2:22][C:23]1[N:28]=[C:27](Cl)[N:26]=[C:25]([C:30]([O:32][CH3:33])=[O:31])[C:24]=1[O:34][CH3:35].C(=O)([O-])[O-].[Na+].[Na+].C(#N)C>[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:22][C:23]1[N:28]=[C:27]([C:6]2[CH:7]=[C:2]([F:1])[C:3]([Si:18]([CH3:19])([CH3:20])[CH3:21])=[CH:4][C:5]=2[F:17])[N:26]=[C:25]([C:30]([O:32][CH3:33])=[O:31])[C:24]=1[O:34][CH3:35]

参加物

8

反応物 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 52270701Methyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylateHCID 71150540(2,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilane

生成物 1

HCID 90408848Methyl 6-amino-2-(2,5-difluoro-4-(trimethylsilyl)phenyl)-5-methoxypyrimidine-4-carboxylate収率 58.9%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
120 °C

実験手順

In a microwave vessel, a suspension of (2,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilane (e.g., WO 2013003740 A1) (1.925 g, 5.05 mmol), methyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate (Head C) (1 g, 4.60 mmol), bis(triphenyl phosphine)palladium(II) chloride (0.323 g, 0.460 mmol) and sodium carbonate (0.584 g, 5.51 mmol) in a 3:1 mixture of acetonitrile (8.62 mL) and water (2.87 mL) was stirred under microwave irradiation (120° C., 20 min). The reaction mixture was poured into an half saturated brine solution and was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title compound as a white solid (0.994 g, 58.9%): mp 130-131° C.; 1H NMR (400 MHz, CDCl3) δ 7.53 (dd, J=8.4, 5.6 Hz, 1H), 7.10 (dd, J=10.2, 4.1 Hz, 1H), 5.44 (s, 2H), 4.00 (s, 3H), 3.94 (s, 3H), 0.32 (d, J=0.9 Hz, 9H); 19F NMR (376 MHz, CDCl3) δ −107.45, −107.51, −122.32, −122.37; ESIMS m/z 367 ([M]+).

後処理

  1. extractionwas extracted with EtOAc (3×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by preparative reverse phase HPLC (water/acetonitrile gradient)

出典と根拠

ORDレコード
ord-eec73b825acb4d44919dea411834ad71
出典データセット
uspto-grants-2015_08
特許番号
US09113629B2

関連ノート

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