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

HRID 220556Notes

Reaction equation

HRID 220556 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[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:28](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[C:17]([CH3:28])=[N:18][N:19]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:15]=3)[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 594382213'-Chloro-4-(3-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinylYield 96.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Stir together 3′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (2.00 g, 10.07 mmol) and 5-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (2.25 g, 12.08 mmol) in dry tetrahydrofuran (10 mL) at room temperature for 10 min., under nitrogen. Add sodium triacetoxyborohydride (3.20 g, 15.10 mmol) and stir reaction for 1 hr. Quench reaction mixture with saturated aq. sodium bicarbonate (30 mL), then extract with DCM (3×20 mL) and pass through an IST Phase Separator Frit®. Concentrate and purify (silica gel chromatography, eluting with 0:100 to 5:95 methanol:DCM). Concentrate and dry in vacuum oven to give the free base as a brown oil (3.585 g, 96.5%). MS (ES): m/z=369 [M+H]+.

Workup

  1. customreaction for 1 hr
  2. customQuench
  3. customreaction mixture with saturated aq. sodium bicarbonate (30 mL)
  4. extractionextract with DCM (3×20 mL)
  5. concentrationConcentrate
  6. custompurify
  7. wash(silica gel chromatography, eluting with 0:100 to 5:95 methanol:DCM)
  8. concentrationConcentrate
  9. customdry in vacuum oven

Sources & evidence

ORD record
ord-30f3c4039885447fa9638ef4e1e44854
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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