Sodium Hydroxide → 3'-Chloro-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine

HRID 220548Notes

Reaction equation

HRID 220548 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][N:15]1[CH:19]=[C:18]([CH:20]=O)[C:17]([CH3:22])=[N:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl>[Cl:1][C:2]1[C:3]([N:8]2[CH2:9][CH2:10][N:11]([CH2:20][C:18]3[C:17]([CH3:22])=[N:16][N:15]([CH3:14])[CH:19]=3)[CH2:12][CH2:13]2)=[N:4][CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 8472851,3-dimethyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 140864382-Chloro-3-(piperazin-1-yl)pyrazine

Product 1

HCID 866416563'-Chloro-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazineYield 46.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 3′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (3 g, 15.1 mmol, 1 eq) and 1,3-dimethyl-1H-pyrazole-4-carbaldehyde (2.0 g, 16.6 mmol, 1.1 eq) in 1,2-dichloroethane (75 mL) add sodium triacetoxyborohydride (4.8 g, 22.6 mmol, 1.5 eq) and stir at room temperature over the weekend. Add 2 N sodium hydroxide (100 mL), separate the layers, extract the aq. layer twice with DCM (75 mL), dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 10:90 methanol:DCM). Combine only the fractions which contain the main component and concentrate to give 3′-chloro-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl as a viscous yellow oil (2.14 g, 46%). Combine all other fractions which contain main component plus impurities, concentrate then repeat the chromatography step to recover further material (1.6 g, 35%, total yield 81%). MS (ES): m/z=307.1 [M+H]+.

Workup

  1. customseparate the layers
  2. extractionextract the aq. layer twice with DCM (75 mL)
  3. dry with materialdry (magnesium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate
  6. custompurify
  7. wash(silica gel chromatography, eluting with 0:100 to 10:90 methanol:DCM)
  8. concentrationconcentrate

Sources & evidence

ORD record
ord-fd6b56d8ad3341048b65998ef8d80107
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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