N,N-二异丙基乙胺 → 2-[6-(3,3-Difluoroazetidin-1-yl)pyrimidin-4-yl]-4-pyridin-3-yl-1,2-dihydro-3H-pyrazol-3-one hydrochloride

HRID 37910

反应方程式

HRID 37910 反应方程式
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[C:12](=[O:13])[C:11]([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)=[CH:10][NH:9]2)[CH:3]=1.C(N(CC)C(C)C)(C)C.Cl.[F:30][C:31]1([F:35])[CH2:34][NH:33][CH2:32]1>C(O)C>[ClH:1].[F:30][C:31]1([F:35])[CH2:34][N:33]([C:2]2[N:7]=[CH:6][N:5]=[C:4]([N:8]3[C:12](=[O:13])[C:11]([C:14]4[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=4)=[CH:10][NH:9]3)[CH:3]=2)[CH2:32]1

参与物

5

反应物 3

HCID 81531N,N-二异丙基乙胺HCID 27582473,3-二氟三甲叉亚胺 盐酸盐HCID 866723282-(6-Chloropyrimidin-4-yl)-4-pyridin-3-yl-1,2-dihydro-3H-pyrazol-3-one

产物 1

HCID 708727812-[6-(3,3-Difluoroazetidin-1-yl)pyrimidin-4-yl]-4-pyridin-3-yl-1,2-dihydro-3H-pyrazol-3-one hydrochloride

试剂、催化剂与溶剂 1

HCID 702乙醇溶剂

实验过程

100 mg (0.4 mmol) of the compound from Example 23, 94 mg (0.7 mmol) of N,N-diisopropylethylamine and 95 mg (0.731 mmol) of 3,3-difluoroazetidine hydrochloride are suspended in 3 ml of ethanol and reacted at 120° C. in a single-mode microwave oven (CEM Explorer) for 40 min. The solvent is then removed, and the residue is taken up in 6 ml of DMSO. Undissolved components are removed by filtration, and the solution obtained is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product-containing fractions are combined and concentrated on a rotary evaporator, and the residue is dried under high vacuum. The residue is then stirred in 5 ml of a 4 N solution of hydrogen chloride in dioxane for 30 min. The solid is filtered off, washed with tert-butyl methyl ether and dried under high vacuum.

后处理

  1. customreacted at 120° C. in a single-mode microwave oven (CEM Explorer) for 40 min
  2. customThe solvent is then removed
  3. customUndissolved components are removed by filtration
  4. customthe solution obtained
  5. customis purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
  6. concentrationconcentrated on a rotary evaporator
  7. customthe residue is dried under high vacuum
  8. filtrationThe solid is filtered off
  9. washwashed with tert-butyl methyl ether
  10. customdried under high vacuum

来源与证据

ORD记录
ord-850c31b799284b4293d5c40f3752ee2b
来源数据集
uspto-grants-2013_09
专利号
US08524699B2

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