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

HRID 220579Notes

Reaction equation

HRID 220579 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[C:16]([CH3:22])=[N:17][N:18]([CH2:20][CH3:21])[CH:19]=3)[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:29]([NH:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1)(=[O:31])[CH3:30].[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].[CH2:20]([N:18]1[CH:19]=[C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:3]3[C:2]([C:37]4[CH:38]=[CH:39][C:34]([CH2:33][NH:32][C:29](=[O:31])[CH3:30])=[CH:35][CH:36]=4)=[N:7][CH:6]=[CH:5][N:4]=3)[CH2:9][CH2:10]2)[C:16]([CH3:22])=[N:17]1)[CH3:21]

Participants

11

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 223094544-[(Acetylamino)methyl]benzeneboronic acidHCID 866416653'-chloro-4-(1-ethyl-3-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

Product 1

HCID 68596658N-{4-[4-(1-Ethyl-3-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-acetamide hydrochlorideYield 57.5%

Reagents, catalysts & solvents 6

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

Procedure

Dissolve 3′-chloro-4-(1-ethyl-3-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.204 g, 0.636 mmol) in tetrahydrofuran (1.75 mL) and water (0.9 mL). Add potassium carbonate (0.193 g, 1.40 mmol) then 4-acetamidomethylbenzeneboronic acid (0.172 g, 0.890 mmol) and degas with nitrogen for 15 min. Add tri-n-butylphosphine tetrafluoroborate (7.4 mg, 0.0254 mmol) and tris(dibenzylideneacetone)dipalladium(0) (12 mg, 0.0127 mmol) and reflux for 20 hr. Cool to room temperature then dilute with saturated aq. sodium bicarbonate and extract 3 times with ethyl acetate. Dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 4.5:95.5 methanol (with 2 M ammonia):DCM), to give a yellow solid. Dissolve the solid 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 (0.172 g, 51%). MS (ES): m/z [M+H]=434

Workup

  1. extractionextract 3 times with ethyl acetate
  2. dry with materialDry (sodium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 4.5:95.5 methanol (with 2 M ammonia):DCM)
  7. customto give a yellow solid
  8. customthen sonicate the mixture for 10 min
  9. customEvaporate the solution

Sources & evidence

ORD record
ord-df20837f1cfb48c0a066d732e76e5cec
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

Loading…