Dimethylformamide → 5-[3-oxo-2-(6-piperidin-1-ylpyrimidin-4-yl)-2,3-dihydro-1H-pyrazol-4-yl]pyridine-3-carbonitrile hydrochloride

HRID 37906Notes

Reaction equation

HRID 37906 reaction equation
[ClH:1].Br[C:3]1[CH:4]=[C:5]([C:9]2[C:10](=[O:26])[N:11]([C:14]3[CH:19]=[C:18]([N:20]4[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]4)[N:17]=[CH:16][N:15]=3)[NH:12][CH:13]=2)[CH:6]=[N:7][CH:8]=1.[CH3:27][N:28](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[O:26]=[C:10]1[C:9]([C:5]2[CH:4]=[C:3]([C:27]#[N:28])[CH:8]=[N:7][CH:6]=2)=[CH:13][NH:12][N:11]1[C:14]1[CH:19]=[C:18]([N:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[N:17]=[CH:16][N:15]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 708727884-(5-Bromopyridin-3-yl)-2-(6-piperidin-1-ylpyrimidin-4-yl)-1,2-dihydro-3H-pyrazol-3-one hydrochloride

Product 1

HCID 708728725-[3-oxo-2-(6-piperidin-1-ylpyrimidin-4-yl)-2,3-dihydro-1H-pyrazol-4-yl]pyridine-3-carbonitrile hydrochloride

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

100 mg (0.2 mmol) of the compound from Example 42, 20 mg (0.2 mmol) of zinc cyanide and 8 mg (0.007 mmol) of tetrakis(triphenylphosphine)palladium in 2 ml DMF are reacted for a total of 75 min at 220° C. in a single-mode microwave oven (Emrys Optimizer). After cooling to RT, the reaction mixture is concentrated under reduced pressure and the residue is taken up in formic acid and purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with 0.1% formic acid added to the water). The resulting formate salt is converted by addition of 0.5 ml of a 4 N solution of hydrogen chloride in dioxane into the hydrochloride. The product is washed first with ethyl acetate and then with diethyl ether and dried under reduced pressure.

Workup

  1. concentrationthe reaction mixture is concentrated under reduced pressure
  2. custompurified by preparative HPLC (RP18 column
  3. additionmobile phase: acetonitrile/water gradient with 0.1% formic acid added to the water)
  4. additionThe resulting formate salt is converted by addition of 0.5 ml of a 4 N solution of hydrogen chloride in dioxane into the hydrochloride
  5. washThe product is washed first with ethyl acetate
  6. dry with materialwith diethyl ether and dried under reduced pressure

Sources & evidence

ORD record
ord-3ed32c01c6c842258033c38cfb0c2278
Source dataset
uspto-grants-2013_09
Patent number
US08524699B2

Reaction notes

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