Water → N-{4-[4-(1-Ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-methanesulfonamide hydrochloride

HRID 220583Notes

Reaction equation

HRID 220583 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][S:30]([NH:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1)(=[O:32])=[O:31].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:38]4[CH:39]=[CH:40][C:35]([CH2:34][NH:33][S:30]([CH3:29])(=[O:31])=[O:32])=[CH:36][CH:37]=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 22309452[4-(Methanesulfonamidomethyl)phenyl]boronic acid2×HCID 866416643'-chloro-4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

Product 1

HCID 68597904N-{4-[4-(1-Ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-methanesulfonamide hydrochlorideYield 85%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 31374DimethylacetamideSolvent

Conditions

Temperature
70 °C

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-methanesulfonylaminomethylphenyl)boronic acid (0.257 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. Continue to heat at 70° C. for 18 hr. Add (4-methanesulfonylaminomethylphenyl) boronic acid (0.129 g, 0.56 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.011 g, 0.009 mmol) and heat to 115° C. for 6 hr. Continue to stir at ambient temperature over 72 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 (371 mg, 85%). Dissolve the free base (0.367 g, 0.781 mmol) in acetonitrile (938 μL) and add aq. 1 N HCl solution (938 μL, 0.938 mmol). Shake for 15 min. at ambient temperature. Freeze dry to give the title compound (397 mg, 100%). MS (ES): m/z=470 [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-b6bb829bc2f64100a150fd5b3806118f
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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