3-氨基吡啶 → HCID 57625991，化合物

HRID 546570

反应方程式

HRID 546570 反应方程式
[NH2:1][C@H:2]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:3]([NH:5][C:6]1[CH:11]=[C:10]([N:12]2[C:16](=[O:17])[C:15]([CH3:19])([CH3:18])[N:14]([CH2:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23](Cl)[CH:22]=3)[C:13]2=[O:28])[CH:9]=[CH:8][C:7]=1[O:29][C:30]([F:33])([F:32])[F:31])=[O:4].[NH2:40][C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1.CC1(C)C2C=CC(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=2OC2C1=CC=C(P(C1C=CC=CC=1)C1C=CC=CC=1)C=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C@H:2]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:3]([NH:5][C:6]1[CH:11]=[C:10]([N:12]2[C:16](=[O:17])[C:15]([CH3:19])([CH3:18])[N:14]([CH2:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:40][C:41]4[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=4)[CH:22]=3)[C:13]2=[O:28])[CH:9]=[CH:8][C:7]=1[O:29][C:30]([F:33])([F:32])[F:31])=[O:4]

参与物

7

反应物 4

HCID 100093-氨基吡啶HCID 10796碳酸氢铯HCID 86628973(9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine)HCID 86629090(2R)-2-amino-N-[5-{3-[(2-chloropyridin-4-yl)methyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl}-2-(trifluoromethoxy)phenyl]-2-phenylacetamide

产物 1

HCID 57625991HCID 57625991，化合物收率 33%

试剂、催化剂与溶剂 2

HCID 167845palladium acetate催化剂HCID 312751,4-二氧六环溶剂

反应条件

温度
110 °C

实验过程

To a solution of 33 mg of (2R)-2-amino-N-[5-{3-[(2-chloropyridin-4-yl)methyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl}-2-(trifluoromethoxy)phenyl]-2-phenylacetamide obtained in stage d) below in 1 mL of dioxane are successively added, under argon, 7 mg of 3-aminopyridine, 3 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) (Xantphos), 1.1 mg of palladium acetate and 61 mg of caesium carbonate. The reaction mixture is heated at 110° C. for 1 hour, filtered and washed with twice 10 mL of dioxane, and the filtrate is then concentrated under reduced pressure. The residue is taken up in 1 mL of dioxane, 1 mL of a 4N solution of hydrogen chloride in dioxane is then added and the reaction mixture is stirred at 40° C. for 2 hours. The reaction mixture is then treated with 30 mL of saturated sodium hydrogen carbonate solution and extracted with three times 30 mL of ethyl acetate. The combined organic phases are then washed with water, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue is purified by HPLC (gradient: water/acetonitrile containing 0.1% formic acid) to give 12 mg of (2R)-2-amino-N-[5-(4,4-dimethyl-2,5-dioxo-3-{[2-(pyridin-3-ylamino)pyridin-4-yl]methyl}imidazolidin-1-yl)-2-(trifluoromethoxy)phenyl]-2-phenylacetamide, the characteristics of which are as follows:

后处理

  1. filtrationfiltered
  2. washwashed with twice 10 mL of dioxane
  3. concentrationthe filtrate is then concentrated under reduced pressure
  4. addition1 mL of a 4N solution of hydrogen chloride in dioxane is then added
  5. additionThe reaction mixture is then treated with 30 mL of saturated sodium hydrogen carbonate solution
  6. extractionextracted with three times 30 mL of ethyl acetate
  7. washThe combined organic phases are then washed with water
  8. dry with materialdried over magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue is purified by HPLC (gradient: water/acetonitrile containing 0.1% formic acid)

来源与证据

ORD记录
ord-e849ff23d4d94254b131dd196d4a2a13
来源数据集
uspto-grants-2011_05
专利号
US07935819B2

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