Potassium Carbonate → 2-{4-[3'-(4-Methoxymethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-ylmethyl]-pyrazol-1-yl}-ethanol hydrochloride

HRID 220578Notes

Reaction equation

HRID 220578 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]([CH2:20][CH2:21][OH:22])[CH:19]=3)[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.[Cl-].[NH4+]>O1CCCC1.O.C(=O)(O)[O-].[Na+].CO.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].F[B-](F)(F)F.C(P(CCCC)CCCC)CCC>[ClH:1].[CH3:29][O:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:2]2[C:3]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][C:15]4[CH:16]=[N:17][N:18]([CH2:20][CH2:21][OH:22])[CH:19]=4)[CH2:10][CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:34][CH:33]=1

Participants

11

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 37238124-(Methoxymethyl)benzeneboronic acidHCID 594382452-[4-(3'-Chloro-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-ylmethyl)-pyrazol-1-yl]-ethanol

Product 1

HCID 685954092-{4-[3'-(4-Methoxymethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-ylmethyl]-pyrazol-1-yl}-ethanol hydrochlorideYield 75%

Reagents, catalysts & solvents 6

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 71317416Tributyl phosphine tetrafluoroborateCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Dissolve 2-[4-(3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-ylmethyl)-pyrazol-1-yl]-ethanol (0.201 g, 0.623 mmol) in tetrahydrofuran (1.7 mL) and water (0.9 mL). Add potassium carbonate (189 mg, 1.37 mmol) then 4-methoxymethylbenzeneboronic acid (145 mg, 0.872 mmol) and degas with nitrogen for 15 min. Add tri-n-butylphosphine tetrafluoroborate (7.2 mg, 0.0249 mmol) and tris(dibenzylideneacetone)dipalladium(0) (11.4 mg, 0.0124 mmol) and microwave at 150° C. for 15 min. Cool to room temperature then dilute with saturated aq. sodium bicarbonate and extract 6 times with ethyl acetate. Dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 6:94 methanol (with 2 M ammonia):DCM), to give a yellow oil. Dissolve the oil in methanol and add ammonium chloride (1 equivalent) then sonicate the mixture for 10 min. Evaporate the solution to give the title compound as a yellow solid (0.191 g, 75%). MS (ES): m/z=409 [M+H]+.

Workup

  1. extractionextract 6 times with ethyl acetate
  2. dry with materialDry (sodium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 6:94 methanol (with 2 M ammonia):DCM)
  7. customto give a yellow oil
  8. customthen sonicate the mixture for 10 min
  9. customEvaporate the solution

Sources & evidence

ORD record
ord-fef102ddfe9e45a29dc7d9107b8f3d77
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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