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

HRID 220532Notes

Reaction equation

HRID 220532 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:5]=[C:6](B(O)O)[CH:7]=[CH:8][CH:9]=1.Cl[C:16]1[C:17]([N:22]2[CH2:27][CH2:26][N:25]([CH2:28][C:29]3[C:30]([CH3:35])=[N:31][N:32]([CH3:34])[CH:33]=3)[CH2:24][CH2:23]2)=[N:18][CH:19]=[CH:20][N:21]=1.CN(C)C(=O)C.C(=O)([O-])[O-].[K+].[K+]>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.O>[CH3:34][N:32]1[CH:33]=[C:29]([CH2:28][N:25]2[CH2:24][CH2:23][N:22]([C:17]3[C:16]([C:6]4[CH:7]=[CH:8][CH:9]=[C:4]([O:3][C:2]([F:14])([F:13])[F:1])[CH:5]=4)=[N:21][CH:20]=[CH:19][N:18]=3)[CH2:27][CH2:26]2)[C:30]([CH3:35])=[N:31]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31374Dimethylacetamide2×HCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 866416563'-Chloro-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine

Product 1

HCID 593217454-(1,3-Dimethyl-1H-pyrazol-4-ylmethyl)-3'-(3-trifluoromethoxyphenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazineYield 35.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
110 °C

Procedure

Charge a carousel tube with 3-(trifluoromethoxy)benzeneboronic acid (140 mg, 0.68 mmol), 3′-chloro-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (173 mg, 0.56 mmol) and N,N-dimethylacetamide (1 mL). Add N,N-dimethylacetamide (3 mL) and potassium carbonate (190 mg, 1.35 mmol) and purge with nitrogen for about 45 min. Add water (2 mL, purged with nitrogen for 1 hr.), then tetrakis(triphenylphosphine)palladium(0) (0.004 g, 0.0034 mmol), purge the reaction for about 30 min., and then heat overnight at 110° C. Cool to room temperature, add water and extract with DCM (3×30 mL). Concentrate the combined DCM extracts and purify using silica gel chromatography followed by reverse phase HPLC to give the title compound (0.087 g, 30%). MS (ES): m/z=433.1 [M+H]+.

Workup

  1. customthe reaction for about 30 min.
  2. temperatureCool to room temperature
  3. extractionextract with DCM (3×30 mL)
  4. concentrationConcentrate the combined DCM extracts
  5. custompurify

Sources & evidence

ORD record
ord-1a0d720bbda240e49a11d1ceb1c209c4
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

Loading…