Triethylamine → (R)-5-(2-(2-aminopyrimidin-5-yl)ethynyl)-N-(2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluorobenzamide

HRID 502689ノート

反応式

HRID 502689 の反応式
[C:1]([C:3]1[CH:4]=[N:5][C:6]([NH2:9])=[N:7][CH:8]=1)#[CH:2].[Si:10]([O:17][C@@H:18]1[CH2:23][CH2:22][CH2:21][N:20]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:25]=2[NH:34][C:35](=[O:44])[C:36]2[CH:41]=[C:40](I)[CH:39]=[CH:38][C:37]=2[F:43])[CH2:19]1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].C(N(CC)CC)C>CC#N.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.[Cu]I>[NH2:9][C:6]1[N:7]=[CH:8][C:3]([C:1]#[C:2][C:40]2[CH:39]=[CH:38][C:37]([F:43])=[C:36]([CH:41]=2)[C:35]([NH:34][C:25]2[CH:26]=[C:27]([C:30]([F:31])([F:32])[F:33])[CH:28]=[CH:29][C:24]=2[N:20]2[CH2:21][CH2:22][CH2:23][C@@H:18]([O:17][Si:10]([C:13]([CH3:14])([CH3:15])[CH3:16])([CH3:11])[CH3:12])[CH2:19]2)=[O:44])=[CH:4][N:5]=1

参加物

7

反応物 3

HCID 8471TriethylamineHCID 161090215-Ethynylpyrimidin-2-amineHCID 68463440(R)-N-(2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluoro-5-iodobenzamide

生成物 1

HCID 68459566(R)-5-(2-(2-aminopyrimidin-5-yl)ethynyl)-N-(2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluorobenzamide

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6342Acetonitrile溶媒

反応条件

温度
70 °C

実験手順

In a 16×120 mm resealable pyrex tube, 5-ethynylpyrimidin-2-amine (0.080 g, 0.67 mmol), (R)-N-(2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluoro-5-iodobenzamide (0.210 g, 0.34 mmol), Bis(triphenylphosphine)palladium(II) dichloride (0.012 g, 0.017 mmol), and Copper(I) iodide (0.0032 g, 0.017 mmol) were taken up in CH3CN and Triethylamine (0.71 ml, 5.1 mmol) was added, and the tube was flushed with nitrogen. The tube was sealed and the reaction heated to 70° C. overnight. The reaction was cooled, and transferred to a 50 mL RBF with EtOAc. The mixture was concentrated in vacuo, and the resulting solid was treated with 10% MeOH in CH2Cl2 and adsorbed onto 1.5 g silica gel and passed through a Redi-Sep®D pre-packed silica gel column (40 g) eluting with 0-60% EtOAc/hexane. The product-containing fractions were concentrated to afford (R)-5-(2-(2-aminopyrimidin-5-yl)ethynyl)-N-(2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluorobenzamide as an off-white solid.

後処理

  1. customthe tube was flushed with nitrogen
  2. customThe tube was sealed
  3. temperatureThe reaction was cooled
  4. concentrationThe mixture was concentrated in vacuo
  5. additionthe resulting solid was treated with 10% MeOH in CH2Cl2
  6. washeluting with 0-60% EtOAc/hexane
  7. concentrationThe product-containing fractions were concentrated

出典と根拠

ORDレコード
ord-ed4f4040ed114033ac3583db24dbfc4f
出典データセット
uspto-grants-2010_08
特許番号
US07776869B2

反応ノート

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