Potassium Fluoride → Methyl 2-chloro-4-methyl-6-(1-methyl-1H-pyrazol-4-yl)pyrimidine-5-carboxylate

HRID 711442Notes

Reaction equation

HRID 711442 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([O:11][CH3:12])=[O:10])=[C:4]([CH3:13])[N:3]=1.[CH3:14][N:15]1[CH:19]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:17]=[N:16]1.[F-].[K+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[N:3]=[C:4]([CH3:13])[C:5]([C:9]([O:11][CH3:12])=[O:10])=[C:6]([C:18]2[CH:17]=[N:16][N:15]([CH3:14])[CH:19]=2)[N:7]=1

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57531614Methyl 2,4-dichloro-6-methylpyrimidine-5-carboxylate

Product 1

HCID 58317739Methyl 2-chloro-4-methyl-6-(1-methyl-1H-pyrazol-4-yl)pyrimidine-5-carboxylateYield 31.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 2,4-dichloro-6-methylpyrimidine-5-carboxylate (0.79 g, 3.57 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.595 g, 2.86 mmol) and bis(triphenylphosphine)palladium chloride (0.050 g, 0.071 mmol) in dioxane (5 mL) was stirred at RT for 10 min, after which potassium fluoride (1.038 g, 17.87 mmol) was added. The mixture was stirred under a nitrogen atmosphere and heated at 90° C. for 12 h. The reaction mixture was filtered through a bed of Celite 545, rinsed with DCM and a small amount of MeOH. Following solvent removal, the residue was dispersed in DMSO/MeOH (1/1) and purified via reverse phase preparative HPLC to give the title compound (237 mg, 25%). [M+H] calc'd for C11H11ClN4O2, 267. found, 267.

Workup

  1. stirringThe mixture was stirred under a nitrogen atmosphere
  2. temperatureheated at 90° C. for 12 h
  3. filtrationThe reaction mixture was filtered through a bed of Celite 545
  4. washrinsed with DCM
  5. customFollowing solvent removal
  6. additionthe residue was dispersed in DMSO/MeOH (1/1)
  7. custompurified via reverse phase preparative HPLC

Sources & evidence

ORD record
ord-991630e5008b4f47bd47f9808348cf80
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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