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

HRID 37907Notes

Reaction equation

HRID 37907 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][O: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].[N:20]1([C:18]2[N:17]=[CH:16][N:15]=[C:14]([N:11]3[C:10](=[O:26])[C:9]([C:5]4[CH:4]=[C:3]([C:27]#[N:28])[CH:8]=[N:7][CH:6]=4)=[CH:13][NH:12]3)[CH:19]=2)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 708726644-(5-Bromopyridin-3-yl)-2-(6-morpholin-4-ylpyrimidin-4-yl)-1,2-dihydro-3H-pyrazol-3-one hydrochloride

Product 1

HCID 708729185-[2-(6-Morpholin-4-ylpyrimidin-4-yl)-3-oxo-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 43, 20 mg (0.2 mmol) of zinc cyanide and 8 mg (0.007 mmol) of tetrakis(triphenylphosphine)palladium in 2 ml DMF are reacted at 220° C. in a single-mode microwave oven (Emrys Optimizer) for a total of 105 min. 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 into the hydrochloride by addition of 0.5 ml of a 4 N solution of hydrogen chloride in dioxane.

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 into the hydrochloride by addition of 0.5 ml of a 4 N solution of hydrogen chloride in dioxane

Sources & evidence

ORD record
ord-abdfca2ac9684aa8b3bd4b6990ea5e38
Source dataset
uspto-grants-2013_09
Patent number
US08524699B2

Reaction notes

Loading…