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

HRID 220547

Reaction equation

HRID 220547 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)[CH:17]=[N:16]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]([CH2:20][C:18]3[CH:17]=[N:16][N:15]([CH3:14])[CH:19]=3)[CH2:12][CH2:13]2)=[N:4][CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 5731171-Methyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 140864382-Chloro-3-(piperazin-1-yl)pyrazine

Product 1

HCID 866416573'-Chloro-4-(1-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazineYield 102.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Dissolve 3′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (3.43 g, 17.3 mmol) in tetrahydrofuran (100 mL). Add 1-methyl-1H-pyrazole-4-carbaldehyde (2.244 g, 20.38 mmol) in dry tetrahydrofuran (5 mL), stir for 10 min. at room temperature, add sodium triacetoxyborohydride (4.32 g, 20.4 mmol), subject the reaction to ultrasound and stir for 6 hr. at room temperature. Add saturated aq. sodium hydrogen carbonate (100 mL) then 2 N sodium hydroxide (10 mL) to the mixture and extract with DCM (2×200 mL). Pass the combined DCM extracts through an IST Phase Separator Frit®, concentrate and purify (silica gel chromatography, eluting with 0:100 to 8:92 methanol:DCM), to give 3′-chloro-4-(1-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl as a crystalline solid (5.21 g, 92%). MS (ES): m/z=293.1 [M+H]+.

Workup

  1. customthe reaction
  2. customat room temperature
  3. extractionAdd saturated aq. sodium hydrogen carbonate (100 mL) then 2 N sodium hydroxide (10 mL) to the mixture and extract with DCM (2×200 mL)
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 0:100 to 8:92 methanol:DCM)

Sources & evidence

ORD record
ord-093f232d605a4f1a9f7c5a1352d3f443
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Linked notes

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