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

HRID 220550Notes

Reaction equation

HRID 220550 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.[C:14]1([N:20]2[CH:24]=[C:23]([CH:25]=O)[CH:22]=[N:21]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.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]([CH2:25][C:23]3[CH:22]=[N:21][N:20]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:24]=3)[CH2:12][CH2:13]2)=[N:4][CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 9520891-Phenyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 140864382-Chloro-3-(piperazin-1-yl)pyrazine

Product 1

HCID 866416623'-chloro-4-(1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinylYield 76%

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 1-phenyl-1H-pyrazole-4-carbaldehyde (2.17 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. Evaporate the ammonia methanol solution and purify (silica gel chromatography, eluting with 0:100 then 5:95 methanol:DCM). Concentrate, wash with diethyl ether and dry in vacuum oven to give 3′-chloro-4-(1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl as brown powder (2.25 g, 76%). MS (ES): m/z=355 [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. customEvaporate the ammonia methanol solution
  13. custompurify (silica gel chromatography
  14. washeluting with 0:100
  15. concentrationConcentrate
  16. washwash with diethyl ether
  17. customdry in vacuum oven

Sources & evidence

ORD record
ord-dae727cb3c99481fbfb09857c2c9e5e6
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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