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

HRID 37909

Reaction equation

HRID 37909 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.[NH:30]1[CH2:33][CH:32]([OH:34])[CH2:31]1.C(O)C>C1COCC1>[ClH:1].[OH:34][CH:32]1[CH2:33][N:30]([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)[CH2:31]1

Participants

6

Reactant 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 866723282-(6-Chloropyrimidin-4-yl)-4-pyridin-3-yl-1,2-dihydro-3H-pyrazol-3-one

Product 1

HCID 708727842-[6-(3-Hydroxyazetidin-1-yl)pyrimidin-4-yl]-4-pyridin-3-yl-1,2-dihydro-3H-pyrazol-3-one hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

100 mg (0.4 mmol) of the compound from Example 23, 94 mg (0.7 mmol) of N,N-diisopropylethylamine and 80 mg (0.7 mmol) of azetidin-3-ol hydrochloride are suspended in 3 ml of THF and reacted at 120° C. in a single-mode microwave oven (CEM Explorer) for 20 min. 2 ml of ethanol are then added, and the mixture is again reacted in a single-mode microwave oven (CEM Explorer) for 20 min. The mixture is then reacted initially at 120° C. for a further 60 min and then at 175° C. for 60 min in a single-mode microwave oven (CEM Explorer). The mixture is then separated directly 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 20 min
  2. customthe mixture is again reacted in a single-mode microwave oven (CEM Explorer) for 20 min
  3. customThe mixture is then reacted initially at 120° C. for a further 60 min
  4. customThe mixture is then separated directly by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
  5. concentrationconcentrated on a rotary evaporator
  6. customthe residue is dried under high vacuum
  7. filtrationThe solid is filtered off
  8. washwashed with tert-butyl methyl ether
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-a8806a2401de483eaf298ff07480a40e
Source dataset
uspto-grants-2013_09
Patent number
US08524699B2

Linked notes

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