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HRID2069723

反应详情

EQUATION

反应方程式

HRID 2069723 的结构方程式

REACTANTS

反应物

2
结构：COC(=O)C(C)(C)c1ccc(Nc2cc(-c3cccc(-n4ncc5cc(C(C)(C)C)cc(F)c5c4=O)c3CO)cn(C)c2=O)nc1
HCID59473826

未命名化合物

结构：[H-].[Li+].[OH-]
HCID86597229

未命名化合物

PRODUCTS

生成物

1
结构：Cn1cc(-c2cccc(-n3ncc4cc(C(C)(C)C)cc(F)c4c3=O)c2CO)cc(Nc2ccc(C(C)(C)C(=O)O)cn2)c1=O
HCID46908804

未命名化合物

收率 86%

AUXILIARIES

试剂、催化剂与溶剂

2
结构：O
溶剂HCID962

Water

H2O

结构：C1COCCO1
溶剂HCID31275

1,4-Dioxane

C4H8O2

PROCEDURE

实验过程

2-(6-{5-[3-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-2-oxo-1,2-dihydro-pyridin-3-ylamino}-pyridin-3-yl)-2-methyl-propionic acid methyl ester (390 mg, 0.62 mmol) was dissolved in dioxane (5 ml). Lithium hydroxide monohydride (78 mg, 1.86 mmol) was dissolved in 5 ml of water and added dropwise. The reaction was heated at 50 degrees centigrade for three hours. The reaction mixture was concentrated, ethyl acetate was added and the layers were separated. The aqueous layer was acidified with 1 M HCL. Ethyl acetate was added and the layers were separated. The organic layer was dried and concentrated. Isopropyl acetate was added to the residue and the mixture was heated to form a solution which was cooled to room temperature and allowed to stand at room temperature for several hours. The amorphous solid was filtered and dried to give 325 mg (86%) of 2-(6-{5-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-2-oxo-1,2-dihydro-pyridin-3-ylamino}-pyridin-3-yl)-2-methyl-propionic acid. A portion of this material was recrystallized from acetonitrile to provide a crystalline solid. MS: (M+H)+=612; MP=218.0-220.0° C. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.38 (s, 9 H) 1.46 (s, 6 H) 3.17 (d, J=4.91 Hz, 1 H) 3.60 (s, 3 H) 4.27-4.42 (m, 2 H) 4.57-4.66 (m, 1 H) 7.26 (d, J=8.69 Hz, 1 H) 7.33-7.45 (m, 3 H) 7.54 (s, 2 H) 7.75 (d, J=13.22 Hz, 1 H) 7.87 (s, 1H) 8.18 (d, J=2.27 Hz, 1 H) 8.51 (d, J=2.64 Hz, 1 H) 8.60 (s, 1 H) 8.65 (d, J=1.89 Hz, 1H) 12.35 (br s, 1 H).

WORKUP

后处理

  1. additionadded dropwise
  2. temperatureThe reaction was heated at 50 degrees centigrade for three hours
  3. concentrationThe reaction mixture was concentrated
  4. additionethyl acetate was added
  5. customthe layers were separated
  6. additionEthyl acetate was added
  7. customthe layers were separated
  8. customThe organic layer was dried
  9. concentrationconcentrated
  10. additionIsopropyl acetate was added to the residue
  11. temperaturethe mixture was heated
  12. customto form a solution which
  13. waitto stand at room temperature for several hours
  14. filtrationThe amorphous solid was filtered
  15. customdried