Potassium Carbonate → 3'-(4-chloro-phenyl)-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

HRID 220528Notes

Reaction equation

HRID 220528 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.Cl[C:12]1[C:13]([N:18]2[CH2:23][CH2:22][N:21]([CH2:24][C:25]3[C:26]([CH3:31])=[N:27][N:28]([CH3:30])[CH:29]=3)[CH2:20][CH2:19]2)=[N:14][CH:15]=[CH:16][N:17]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:12]2[C:13]([N:18]3[CH2:23][CH2:22][N:21]([CH2:24][C:25]4[C:26]([CH3:31])=[N:27][N:28]([CH3:30])[CH:29]=4)[CH2:20][CH2:19]3)=[N:14][CH:15]=[CH:16][N:17]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 866416563'-Chloro-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine

Product 1

HCID 593217723'-(4-chloro-phenyl)-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinylYield 54.2%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

Add 4-chlorobenzeneboronic acid (64 mg, 0.41 mmol) to a mixture 3′-chloro-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (104 mg, 0.34 mmol), potassium carbonate (113 mg, 0.82 mmol) and tetrakis(triphenylphosphine) palladium(0) (0.002 g, 0.002 mmol) in N,N-dimethylacetamide (2 mL) and water (1 mL). Purge with nitrogen and heat overnight at 110° C. Cool to room temperature add water (10 mL), extract with DCM (3×20 mL) combine and purify using high pH reverse phase HPLC to give 3′-(4-chloro-phenyl)-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (68 mg, 54.2%). MS (ES): m/z=383 [M+H]+.

Workup

  1. customPurge with nitrogen
  2. temperatureCool to room temperature
  3. additionadd water (10 mL)
  4. extractionextract with DCM (3×20 mL) combine
  5. custompurify

Sources & evidence

ORD record
ord-8b129fb1e82b43c48754a24d33e967c6
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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