Sodium Carbonate → 2-[2-(4-aminophenyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-ol

HRID 1095416ノート

反応式

HRID 1095416 の反応式
Cl[C:2]1[N:7]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[N:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C(Cl)Cl.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>[NH2:31][C:30]1[CH:32]=[CH:33][C:27]([C:2]2[N:7]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]3[CH3:18])[N:3]=2)=[CH:28][CH:29]=1

参加物

8

反応物 3

HCID 10340Sodium CarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 593801562-[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-ol

生成物 1

HCID 595083982-[2-(4-aminophenyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-ol収率 60.4%

試薬・触媒・溶媒 4

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

Dichlorobis(triphenylphosphine)palladium(II) (0.492 g, 0.70 mmol) was added to 2-[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-ol (3.81 g, 14.02 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (3.38 g, 15.42 mmol) and sodium carbonate (4.46 g, 42.06 mmol) in DME (80 mL) and water (20.00 mL) under nitrogen. The resulting solution was stirred at 80° C. for 6 hours. The reaction mixture was diluted with DCM (200 mL), and washed with water (400 mL) twice. The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20 to 60% ethyl acetate in isohexane, to give a material which was further purified by ion exchange chromatography using an SCX column, eluting with 2M ammonia in methanol, to give the desired material as a pink gum (2.78 g).

後処理

  1. washwashed with water (400 mL) twice
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 20 to 60% ethyl acetate in isohexane
  7. customto give a material which
  8. customwas further purified by ion exchange chromatography
  9. washeluting with 2M ammonia in methanol

出典と根拠

ORDレコード
ord-e54eb3618dd848f2a7878edab3be4807
出典データセット
uspto-grants-2012_03
特許番号
US08138183B2

反応ノート

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