Hydrochloric Acid → HCID 178434548, compound

HRID 220523Notes

Reaction equation

HRID 220523 reaction equation
[ClH:1].Cl.[C:3]1([C:9]2[C:10]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[N:11][CH:12]=[CH:13][N:14]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:21][C:22]1[C:26]([CH:27]=O)=[CH:25][NH:24][N:23]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].Cl>O1CCCC1.C(#N)C.C(Cl)Cl>[ClH:1].[CH3:21][C:22]1[C:26]([CH2:27][N:18]2[CH2:19][CH2:20][N:15]([C:10]3[C:9]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=4)=[N:14][CH:13]=[CH:12][N:11]=3)[CH2:16][CH2:17]2)=[CH:25][NH:24][N:23]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride2×HCID 685957653'-phenyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochlorideHCID 1784345503-methyl-1H-pyrazole-4-carbaldehyde2×

Product 1

HCID 178434548HCID 178434548, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 3′-phenyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (0.4 g, 1.28 mmol, 1 eq) and 3-methyl-1H-pyrazole-4-carbaldehyde (0.27 g, 2.45 mmol, 1.92 eq) in tetrahydrofuran (20 mL) add sodium triacetoxyborohydride (0.88 g, 4.15 mmol, 3 eq) in one portion as a solid. Stir the mixture at room temperature under nitrogen for 70 hr. Add a further portion of 3-methyl-1H-pyrazole-4-carbaldehyde (70 mg, 0.639 mmol, 0.5 eq) and sodium triacetoxyborohydride (271 mg, 1.28 mmol, 1 eq) and stir for a further 21 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 flash chromatography on silica gel column, eluting with 5% methanol in DCM, and then 5-10% methanol in DCM. Dissolve this material (157 mg, 0.47 mmol) in the minimum quantity of 50% aqueous acetonitrile. Add 2M aqueous hydrogen chloride (235 μL, 0.47 mmol) and lyophilize to give the title compound (159 mg, 34%). MS (ES): m/z=335.2 [M+H]+.

Workup

  1. stirringstir for a further 21 hr
  2. customseparate
  3. extractionextract the aqueous layer with DCM (20 ml)
  4. dry with materialCombine the organics, dry over magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by flash chromatography on silica gel column
  8. washeluting with 5% methanol in DCM

Sources & evidence

ORD record
ord-27b12cde602148e18e296a89fa0e0da8
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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