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

HRID 220496Notes

Reaction equation

HRID 220496 reaction equation
Cl.Cl.[Cl:3][C:4]1[C:5]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:6][CH:7]=[CH:8][N:9]=1.[CH3:16][N:17]1[C:21]([CH3:22])=[C:20]([CH:23]=O)[C:19]([CH3:25])=[N:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>O1CCCC1>[Cl:3][C:4]1[C:5]([N:10]2[CH2:11][CH2:12][N:13]([CH2:23][C:20]3[C:19]([CH3:25])=[N:18][N:17]([CH3:16])[C:21]=3[CH3:22])[CH2:14][CH2:15]2)=[N:6][CH:7]=[CH:8][N:9]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 7365151,3,5-trimethyl-1H-pyrazole-4-carboxaldehyde2×HCID 5049666Sodium triacetoxyborohydrideHCID 866416583'-chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

Product 1

HCID 866416593'-Chloro-4-(1,3,5-trimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (2.11 g, 7.77 mmol, 1 eq) in tetrahydrofuran (20 mL) add 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde (1.61 g, 11.65 mmol, 1.5 eq). Stir for 10 min and add sodium triacetoxyborohydride (4.20 g, 19.40 mmol, 2.5 eq) in one portion. Stir at room temperature under nitrogen for 1 hr., then add further 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde (0.50 g, 3.6 mmol, 0.47 eq). Stir for 30 min., add saturated aqueous sodium hydrogen carbonate (100 mL) slowly, and then extract with DCM (3×50 mL). Pass the combined DCM extracts through an IST Phase Separator Frit®, concentrate and purify (silica gel chromatography, eluting with 2:98 to 5:95 methanol:DCM), to give the title preparation as a white powder (2.468 g, 98%). MS (ES): m/z=321 [M+H]+.

Workup

  1. stirringStir at room temperature under nitrogen for 1 hr
  2. stirringStir for 30 min.
  3. extractionextract with DCM (3×50 mL)
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 2:98 to 5:95 methanol:DCM)
  7. customto give the title

Sources & evidence

ORD record
ord-af4453e1839241e3ac030c158b6ad5dd
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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