Water → 4-(1-Ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3'-(4-methoxymethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl hydrochloride

HRID 220581Notes

Reaction equation

HRID 220581 reaction equation
[Cl:1][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]([CH2:21][CH3:22])[C:19]=3[CH3:20])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:29][O:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.O>CN(C)C(=O)C.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>[ClH:1].[CH2:21]([N:18]1[C:19]([CH3:20])=[C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:3]3[C:2]([C:35]4[CH:36]=[CH:37][C:32]([CH2:31][O:30][CH3:29])=[CH:33][CH:34]=4)=[N:7][CH:6]=[CH:5][N:4]=3)[CH2:9][CH2:10]2)[CH:16]=[N:17]1)[CH3:22]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 37238124-(Methoxymethyl)benzeneboronic acidHCID 866416643'-chloro-4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

Product 1

HCID 685951804-(1-Ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3'-(4-methoxymethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl hydrochlorideYield 67%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 31374DimethylacetamideSolvent

Procedure

Combine 3′-chloro-4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.300 g, 0.935 mmol), potassium carbonate (0.310 g, 2.24 mmol), 4-methoxymethylphenylboronic acid (0.186 g, 1.12 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.011 g, 0.009 mmol) in N,N-dimethylacetamide (1.9 mL). Add water (940 μL), and reflux reaction for 6 hr. Add DCM and wash with water. Extract water layer three times with DCM. Dry combined organics (magnesium sulfate) and purify (silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate:hexanes then 10:90 to 20:80 methanol:ethyl acetate), to give the free base of the title compound (256 mg, 67%). Dissolve the free base (0.254 g, 0.624 mmol) in acetonitrile (748 μL) and add aq. 1 N HCl solution (748 μL, 0.748 mmol). Shake for 15 min. at ambient temperature. Freeze dry to give the title compound (273 mg, 99%). MS (ES): m/z=407 [M+H]+.

Workup

  1. customreaction for 6 hr
  2. washAdd DCM and wash with water
  3. customDry
  4. custompurify (silica gel chromatography
  5. washeluting with 50:50 to 100:0 ethyl acetate

Sources & evidence

ORD record
ord-bd62cd16721c4a84a30dd723e67ceca9
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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