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

HRID 37910

Reaction equation

HRID 37910 reaction equation
[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

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 866723282-(6-Chloropyrimidin-4-yl)-4-pyridin-3-yl-1,2-dihydro-3H-pyrazol-3-one

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-850c31b799284b4293d5c40f3752ee2b
Source dataset
uspto-grants-2013_09
Patent number
US08524699B2

Linked notes

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