Hydrochloric Acid → 4-(1-Ethyl-3,5-dimethyl-1H-pyrazol-4-ylmethyl)-3'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl hydrochloride

HRID 220524Notes

Reaction equation

HRID 220524 reaction equation
[ClH:1].Cl.[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[N:12][CH:13]=[CH:14][N:15]=2)=[CH:6][CH:5]=1.[CH2:22]([N:24]1[C:28]([CH3:29])=[C:27]([CH:30]=O)[C:26]([CH3:32])=[N:25]1)[CH3:23].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].Cl>O1CCCC1.C(#N)C.C(Cl)Cl>[ClH:1].[CH2:22]([N:24]1[C:28]([CH3:29])=[C:27]([CH2:30][N:19]2[CH2:18][CH2:17][N:16]([C:11]3[C:10]([C:7]4[CH:8]=[CH:9][C:4]([F:3])=[CH:5][CH:6]=4)=[N:15][CH:14]=[CH:13][N:12]=3)[CH2:21][CH2:20]2)[C:26]([CH3:32])=[N:25]1)[CH3:23]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 31574611-Ethyl-3,5-dimethyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 673669583'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

Product 1

HCID 685969504-(1-Ethyl-3,5-dimethyl-1H-pyrazol-4-ylmethyl)-3'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl hydrochlorideYield 15%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (0.3 g, 0.906 mmol, 1 eq) and 1-ethyl-3,5-dimethyl-1H-pyrazole-4-carbaldehyde (207 mg, 1.36 mmol, 1.5 eq) in tetrahydrofuran (10 mL) add sodium triacetoxyborohydride (480 mg, 2.26 mmol, 2.5 eq) in one portion as a solid. Stir the mixture at room temperature under nitrogen for 19 hr. Add 2M aqueous sodium hydroxide solution (10 ml) and DCM (20 ml) separate and extract the aqueous layer with DCM (20 ml). Combine the organics, dry over magnesium sulfate, filter and concentrate. Purify by high pH reverse phase HPLC. Dissolve this material (49 mg, 0.12 mmol), in the minimum quantity of 50% aqueous acetonitrile. Add 2M aqueous hydrogen chloride (60 μL, 0.12 mmol) and lyophilize to give the title compound (58 mg, 15%). MS (ES): m/z=395.2 [M+H]+.

Workup

  1. customseparate
  2. extractionextract the aqueous layer with DCM (20 ml)
  3. dry with materialCombine the organics, dry over magnesium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify by high pH reverse phase HPLC

Sources & evidence

ORD record
ord-b8e8b01beb84434e9f3da647114b4aad
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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