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

HRID 220521Notes

Reaction equation

HRID 220521 reaction equation
[N:1]1([C:7]2[C:12]([C:13]3[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][CH:14]=3)=[N:11][CH:10]=[CH:9][N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:21][N:22]1[C:26]([CH3:27])=[C:25]([CH:28]=O)[C:24]([CH3:30])=[N:23]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+].[OH-].[Na+]>O1CCCC1>[CH3:21][N:22]1[C:26]([CH3:27])=[C:25]([CH2:28][N:4]2[CH2:5][CH2:6][N:1]([C:7]3[C:12]([C:13]4[CH:14]=[CH:15][C:16]([C:17]#[N:18])=[CH:19][CH:20]=4)=[N:11][CH:10]=[CH:9][N:8]=3)[CH2:2][CH2:3]2)[C:24]([CH3:30])=[N:23]1

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 7365151,3,5-trimethyl-1H-pyrazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 685958424-(3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl)-benzonitrile

Product 1

HCID 593220204-(1,3,5-Trimethyl-1H-pyrazol-4-ylmethyl)-3'-(4-cyanophenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazineYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Suspend 4-(3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl)-benzonitrile (0.179 g, 0.675 mmol) in tetrahydrofuran (4 mL). Add 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde (0.098 g, 0.71 mmol) in tetrahydrofuran (490 μL), then sodium triacetoxyborohydride (0.15 g, 0.071 mmol) and stir under nitrogen at room temperature for 3 hr. Add saturated aqueous sodium hydrogen carbonate (10 mL) followed by 2 N sodium hydroxide (1 mL) to the mixture and extract with DCM (3×20 mL). Pass the combined DCM extracts through an IST Phase Separator Frit®, concentrate, and purify (silica gel chromatography, eluting with 0:100 to 12:88 methanol:DCM), to give the title compound (153.5 mg, 59%). MS (ES): m/z=388 [M+H]+.

Workup

  1. extractionextract with DCM (3×20 mL)
  2. concentrationconcentrate
  3. custompurify
  4. wash(silica gel chromatography, eluting with 0:100 to 12:88 methanol:DCM)

Sources & evidence

ORD record
ord-53394937990b4ed28444bc31395766af
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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