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HRID575909

反应详情

EQUATION

反应方程式

HRID 575909 的结构方程式

REACTANTS

反应物

3
结构：CCN(CC)CC
HCID8471

Triethylamine

C6H15N

结构：C#Cc1nc(Br)cnc1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
HCID58070394

未命名化合物

结构：CC(C)(C)OC(=O)N(Cc1ccc(C(Cl)=NO)cc1)C1CCOCC1
HCID86680728

未命名化合物

PRODUCTS

生成物

1
结构：CN(Cc1ccc(-c2cc(-c3nc(Br)cnc3N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)on2)cc1)C(=O)OC(C)(C)C
HCID86690359

未命名化合物

收率 92%

AUXILIARIES

试剂、催化剂与溶剂

2
结构：O
溶剂HCID962

Water

H2O

结构：ClCCl
溶剂HCID6344

Dichloromethane

CH2Cl2

PROCEDURE

实验过程

A suspension of tert-butyl N-(5-bromo-3-ethynylpyrazin-2-yl)-N-tert-butoxycarbonylcarbamate (Compound 4-iii) (1.59 kg, 3.99 mol) and tert-butyl 4-(chloro(hydroxyimino)methyl)benzyl(tetrahydro-2H-pyran-4-yl)carbamate (1.31 kg, 4.39 mol; 1.10 equiv.) in CH2Cl2 (12.7 L) is stirred at ambient temperature. Triethylamine (444 g, 611 mL, 4.39 mol) is added to the suspension and the reaction temperature is maintained between 20-30° C. for 20-48 h to ensure complete reaction. The reaction mixture is diluted with water (8 L) and thoroughly mixed, then the phases are separated. The organic phase is washed with water (8 L), dried (Na2SO4), and then concentrated until about 1 L of CH2Cl2 remains. The concentrate is diluted with heptane (3.2 L) and re-concentrated at 40° C./200 torr until no distillate is observed. The concentrate is stirred and further diluted with heptane (12.7 L) to precipitate a solid. The suspension is stirred overnight. The solid is collected by filtration, washed with heptane (2×3 L) then dried to afford Compound 4-iv (2.42 kg; 92% yield, 100 area % purity by HPLC) as a light tan powder. 1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 7.82 (d, J=8.2 Hz, 2H), 7.31 (m, 3H), 4.46 (br s, 2H), 2.84 (br d, 3H), 1.57 (s, 2H), 1.44 (br s, 9H), 1.36 (s, 18H).

WORKUP

后处理

  1. temperaturethe reaction temperature is maintained between 20-30° C. for 20-48 h
  2. customreaction
  3. additionthoroughly mixed
  4. customthe phases are separated
  5. washThe organic phase is washed with water (8 L)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated until about 1 L of CH2Cl2
  8. additionThe concentrate is diluted with heptane (3.2 L)
  9. concentrationre-concentrated at 40° C./200 torr until no distillate
  10. stirringThe concentrate is stirred
  11. additionfurther diluted with heptane (12.7 L)
  12. customto precipitate a solid
  13. stirringThe suspension is stirred overnight
  14. filtrationThe solid is collected by filtration
  15. washwashed with heptane (2×3 L)
  16. customthen dried
  17. customto afford Compound 4-iv (2.42 kg; 92% yield, 100 area % purity by HPLC) as a light tan powder