5-Methyl-1-phenyl-1H-pyrazole-4-carboxaldehyde → 3'-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

HRID 220551Notes

Reaction equation

HRID 220551 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[CH3:14][C:15]1[N:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:18]=[CH:17][C:16]=1[CH:26]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[Cl:1][C:2]1[C:3]([N:8]2[CH2:9][CH2:10][N:11]([CH2:26][C:16]3[CH:17]=[N:18][N:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:15]=3[CH3:14])[CH2:12][CH2:13]2)=[N:4][CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 27764375-Methyl-1-phenyl-1H-pyrazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 140864382-Chloro-3-(piperazin-1-yl)pyrazine

Product 1

HCID 866416633'-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinylYield 66.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Stir together 3′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (1.6 g, 8.43 mmol) and 5-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (2.35 g, 12.6 mmol) in dry tetrahydrofuran (10 mL) at room temperature for 15 min., under nitrogen. Add sodium triacetoxyborohydride (2.68 g, 12.6 mmol) and stir reaction for 1 hr. Quench reaction mixture with saturated aq. sodium bicarbonate (50 mL), then extract with DCM (3×50 mL) and pass through an IST Phase Separator Frit®. Concentrate and purify (silica gel chromatography, eluting with 5:95 methanol:DCM) and concentrate all fractions containing product. Pass the mixture through a CBA column to retain the product, wash with methanol and then elute with 2 M ammonia in methanol. Recrystallize from hot ethanol and dry in vacuum oven to give 3′-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl as white crystals (2.08 g, 65%). MS (ES): m/z=369 [M+H]+.

Workup

  1. customreaction for 1 hr
  2. customQuench
  3. customreaction mixture with saturated aq. sodium bicarbonate (50 mL)
  4. extractionextract with DCM (3×50 mL)
  5. concentrationConcentrate
  6. custompurify
  7. wash(silica gel chromatography, eluting with 5:95 methanol:DCM)
  8. concentrationconcentrate all fractions
  9. additioncontaining product
  10. washwash with methanol
  11. washelute with 2 M ammonia in methanol
  12. customRecrystallize from hot ethanol
  13. customdry in vacuum oven

Sources & evidence

ORD record
ord-75affb79491841b9a82d6ddfd72bdf93
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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