Sodium Carbonate → 1-((4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)methyl)cyclopropanecarbonitrile

HRID 535746ノート

反応式

HRID 535746 の反応式
[NH2:1][CH2:2][C:3]1([C:6]#[N:7])[CH2:5][CH2:4]1.[Br:8][C:9]1[N:10]=[C:11]([CH:29]2[CH2:31][CH2:30]2)[N:12]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:13]=1[C:14]1[CH:19]=[CH:18][N:17]=[C:16](Cl)[N:15]=1.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[Na+].[Na+]>CN1C(=O)CCC1>[Br:8][C:9]1[N:10]=[C:11]([CH:29]2[CH2:31][CH2:30]2)[N:12]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:27])[CH3:28])[C:13]=1[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([NH:7][CH2:6][C:3]2([C:2]#[N:1])[CH2:5][CH2:4]2)[N:15]=1

参加物

6

反応物 4

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 552821201-(Aminomethyl)cyclopropanecarbonitrileHCID 866514084-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)-2-chloropyrimidine

生成物 1

HCID 698095911-((4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)methyl)cyclopropanecarbonitrile収率 66%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
110 °C

実験手順

A mixture of 1-(aminomethyl)cyclopropanecarbonitrile (0.67 g, 7.0 mmol), 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (2.01 g, 4.7 mmol), DIEA (1.64 ml, 9.35 mmol), Na2CO3 (0.99 g, 9.4 mmol) and NMP (2 mL) was heated at 110° C. for 25 hours. The reaction mixture was allowed to cool to room temperature and partitioned between EtOAc (10 mL) and water (20 mL). The layers were separated and the organic portion was sequentially washed with water (20 mL), brine (10 mL), and concentrated. The resulting residue was purified by flash chromatography on silica gel eluting with an EtOAc-heptane (0-50%) gradient to provide 1-((4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)methyl)cyclopropanecarbonitrile (1.50 g, 3.06 mmol, 66%) as a white foam. LCMS (m/z) 491.1 (MH+), tR=0.99 minute.

後処理

  1. temperatureto cool to room temperature
  2. custompartitioned between EtOAc (10 mL) and water (20 mL)
  3. customThe layers were separated
  4. washthe organic portion was sequentially washed with water (20 mL), brine (10 mL)
  5. concentrationconcentrated
  6. customThe resulting residue was purified by flash chromatography on silica gel eluting with an EtOAc-heptane (0-50%) gradient

出典と根拠

ORDレコード
ord-3d887c1cc4104f8097d826ffeb6b2a1d
出典データセット
uspto-grants-2014_10
特許番号
US08859548B2

反応ノート

読み込み中…