Dimethylformamide → 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-6-chloro-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrile

HRID 1499927ノート

反応式

HRID 1499927 の反応式
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[N:14][C:15]=2[NH2:17])[NH:10][N:9]=1.[Cl:18][C:19]1[C:24]([C:25]#[N:26])=[C:23]([N:27]2[CH2:30][CH:29]([O:31][CH3:32])[CH2:28]2)[C:22]([O:33][CH2:34][CH3:35])=[C:21]([CH:36](Cl)[CH3:37])[CH:20]=1.CN(C)C=O>CCOC(C)=O>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:36]([C:21]3[CH:20]=[C:19]([Cl:18])[C:24]([C:25]#[N:26])=[C:23]([N:27]4[CH2:30][CH:29]([O:31][CH3:32])[CH2:28]4)[C:22]=3[O:33][CH2:34][CH3:35])[CH3:37])[N:9]=[C:8]([CH3:7])[C:16]=12

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 866778446-Chloro-4-(1-chloroethyl)-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrileHCID 178434474HCID 178434474、化合物

生成物 1

HCID 715090894-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-6-chloro-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrile収率 20%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

Cesium carbonate (50 mg, 0.2 mmol) was added to a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (16 mg, 0.10 mmol) and 6-chloro-4-(1-chloroethyl)-3-ethoxy-2-(3-methoxyazetidin-1-yl)benzonitrile (30 mg, 0.09 mmol) in N,N-dimethylformamide (3 mL, 40 mmol) and the reaction was stirred at 80° C. overnight. The mixture was diluted with EtOAc, washed with water, brine, dried over Na2SO4, filtered and concentrated the crude product. The product was purified was purified by prep HPLC on a C-18 column eluting water:acetonitrile gradient buffered pH 10 to give the title compound as a white amorphous solid (0.007 g, 20%). The product was isolated as a racemic mixture. LCMS calculated for C21H25ClN7O2(M+H)+: m/z=442.1; found: 442.1. 1H NMR (400 MHz, DMSO-d6) δ 8.11 (s, 1H), 6.80 (s, 1H), 6.18 (d, J=7.1 Hz, 1H), 4.58-4.44 (m, 2H), 4.18 (m, 1H), 4.13-4.01 (m, 2H), 3.81-3.62 (m, 2H), 3.23 (s, 3H), 2.55 (s, 3H), 1.69 (d, J=7.1 Hz, 3H), 1.35 (t, J=7.0 Hz, 3H).

後処理

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated the crude product
  5. customThe product was purified
  6. customwas purified by prep HPLC on a C-18 column
  7. washeluting water

出典と根拠

ORDレコード
ord-4fde2fc04fa74f73a7dfa6ccf5c1debd
出典データセット
uspto-grants-2015_12
特許番号
US09199982B2

反応ノート

読み込み中…