顺式-1,2-环己二胺 → N-((1R,2S)-2-aminocyclohexyl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246400

反应方程式

HRID 246400 反应方程式
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C@@H:25]1([NH2:32])[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]1[NH2:31].[CH3:33][O:34][C:35]1[CH:36]=[C:37]2[C:41](=[CH:42][CH:43]=1)[N:40]([CH3:44])[N:39]=[C:38]2[C:45]1[N:46]=[C:47]2[C:53]([C:54](O)=[O:55])=[CH:52][N:51]([CH2:57][O:58][CH2:59][CH2:60][Si:61]([CH3:64])([CH3:63])[CH3:62])[C:48]2=[N:49][CH:50]=1>CN(C=O)C>[NH2:31][C@H:26]1[CH2:27][CH2:28][CH2:29][CH2:30][C@H:25]1[NH:32][C:54]([C:53]1[C:47]2[C:48](=[N:49][CH:50]=[C:45]([C:38]3[C:37]4[C:41](=[CH:42][CH:43]=[C:35]([O:34][CH3:33])[CH:36]=4)[N:40]([CH3:44])[N:39]=3)[N:46]=2)[N:51]([CH2:57][O:58][CH2:59][CH2:60][Si:61]([CH3:62])([CH3:64])[CH3:63])[CH:52]=1)=[O:55]

参与物

5

反应物 3

HCID 342917顺式-1,2-环己二胺HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712798522-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

产物 1

HCID 71280458N-((1R,2S)-2-aminocyclohexyl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide收率 21.7%

试剂、催化剂与溶剂 1

HCID 6228N,N-二甲基甲酰胺溶剂

反应条件

温度
25 °C

实验过程

In a 16×100 mm screw cap test tube were added HATU (80.5 mg, 212 μmol.20) and (1R,2S)-cyclohexane-1,2-diamine (20.1 mg, 176 μmol) then 2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (80 mg, 176 μmol) dissolved in DMF (2.00 mL) was added to give a light yellow solution which immediately formed a white precipitated. The reaction mixture stirred at 25° C. overnight, solvents evaporated and residue purified by chromatography (60 g column, 50 μm from Analogix, 0 to 5% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane to give the desired N-((1R,2S)-2-aminocyclohexyl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (21 mg, 38.2 μmol, 21.7%). MS (M+H)+=550 (>90% purity); 1H NMR (CDCl3) δ: 9.02 (s, 1H), 8.51 (s, 1H), 7.51 (s, 1H), 7.43 (d, J=9.1 Hz, 1H), 7.22 (dd, J=9.3, 2.1 Hz, 1H), 5.61-5.84 (m, 2H), 4.78 (br. s., 1H), 4.18 (s, 3H), 4.02 (t, J=3.2 Hz, 1H), 3.91 (s, 3H), 3.76 (br. s., 1H), 3.62-3.71 (m, 2H), 2.09 (br. s., 2H), 2.03 (s, 2H), 1.80-1.98 (m, 4H), 1.52-1.78 (m, 4H), 0.98 (dd, J=9.3, 7.4 Hz, 2H), 0.00 (s, 9H).

后处理

  1. customIn a 16×100 mm screw cap test tube
  2. additionwas added
  3. customto give a light yellow solution which
  4. customimmediately formed a white precipitated
  5. customsolvents evaporated
  6. customresidue purified by chromatography (60 g column, 50 μm from Analogix, 0 to 5% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane

来源与证据

ORD记录
ord-86f34cffcfcb415591490efc35ab6075
来源数据集
uspto-grants-2014_02
专利号
US08658646B2

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