Potassium Carbonate → 4-(1-Methyl-1H-pyrazol-4-ylmethyl)-3'-(2,3-difluorophenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine

HRID 220530Notes

Reaction equation

HRID 220530 reaction equation
Cl[C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[F:27][C:28]1[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O>CN(C)C(=O)C.O.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>[CH3:20][N:18]1[CH:19]=[C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:3]3[C:2]([C:32]4[CH:31]=[CH:30][CH:29]=[C:28]([F:27])[C:33]=4[F:34])=[N:7][CH:6]=[CH:5][N:4]=3)[CH2:9][CH2:10]2)[CH:16]=[N:17]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2734333(2,3-Difluorophenyl)boronic acidHCID 866416573'-Chloro-4-(1-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine

Product 1

HCID 593218894-(1-Methyl-1H-pyrazol-4-ylmethyl)-3'-(2,3-difluorophenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazineYield 26%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

Dissolve 3′-chloro-4-(1-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (160 mg, 0.55 mmol) in N,N-dimethylacetamide (4 mL) and water (2 mL) and purge with nitrogen for 0.5 hr. Add potassium carbonate (180 mg, 1.30 mmol) then 2,3-difluorobenzeneboronic acid (100 mg, 0.66 mmol) and purge with nitrogen for 0.5 hr. Add tetrakis(triphenylphosphine)palladium(0) (0.01 g, 0.0086 mmol) and heat at 110° C. for 3.25 hr. Cool to room temperature and purify (silica gel chromatography, eluting with 0:100 to 30:70 methanol:DCM), followed by reverse phase HPLC to give the title compound (52.69 mg, 26%). MS (ES): m/z=371 [M+H]+.

Workup

  1. custompurge with nitrogen for 0.5 hr
  2. custompurify
  3. wash(silica gel chromatography, eluting with 0:100 to 30:70 methanol:DCM)

Sources & evidence

ORD record
ord-7c1360b80f14449bbf61e12a433225a1
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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