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

HRID 220531Notes

Reaction equation

[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.Cl[C:15]1[C:16]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:29]=[N:30][N:31]([CH3:33])[CH:32]=3)[CH2:23][CH2:22]2)=[N:17][CH:18]=[CH:19][N:20]=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>[CH3:33][N:31]1[CH:32]=[C:28]([CH2:27][N:24]2[CH2:23][CH2:22][N:21]([C:16]3[C:15]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=4)=[N:20][CH:19]=[CH:18][N:17]=3)[CH2:26][CH2:25]2)[CH:29]=[N:30]1

Participants

Conditions

Temperature: 110 °C

Procedure

Charge a carousel tube with 3-trifluoromethylbenzeneboronic acid (136 mg, 0.66 mmol), 3′-chloro-4-(1-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (160 mg, 0.55 mmol) and N,N-dimethylacetamide (1 mL). Add N,N-dimethylacetamide (3 mL) and potassium carbonate (185 mg, 1.32 mmol) and purge with nitrogen for about 45 min. Add water (2 mL, purged with nitrogen for 1 hr.) then tetrakis(triphenylphosphine)palladium(0) (0.003 g, 0.0025 mmol) and purge the reaction vessel for about 30 min. Heat at 110° C. overnight. Cool to room temperature, add water and extract with DCM (3×30 mL), and then concentrate the combined DCM extracts. Purify using silica gel chromatography, followed by reverse phase HPLC, to give the title compound (128 mg, 58%). MS (ES): m/z=403.1 [M+H]+.

Workup

temperatureCool to room temperature
extractionextract with DCM (3×30 mL)
concentrationconcentrate the combined DCM
customPurify

Sources & evidence

ORD record: ord-9f282f01683641508d2828d474c33fda
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08202873B2

Reaction notes

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