Triethylamine → 3'-chloro-4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

HRID 220553Notes

Reaction equation

HRID 220553 reaction equation
[CH2:1]([N:3]1[C:7]([CH3:8])=[C:6]([CH:9]=O)[CH:5]=[N:4]1)[CH3:2].Cl.Cl.[Cl:13][C:14]1[C:15]([N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[N:16][CH:17]=[CH:18][N:19]=1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(O)(=O)C>[Cl:13][C:14]1[C:15]([N:20]2[CH2:21][CH2:22][N:23]([CH2:9][C:6]3[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]=3[CH3:8])[CH2:24][CH2:25]2)=[N:16][CH:17]=[CH:18][N:19]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5732041-Ethyl-5-methyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 866416583'-chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

Product 1

HCID 866416643'-chloro-4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinylYield 88.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolvent

Procedure

Dissolve 1-ethyl-5-methyl-1H-pyrazole-4-carbaldehyde (2.92 g, 21.1 mmol) in 1,2-dichloroethane (184 mL). Add 3′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (4.97 g, 18.3 mmol), triethylamine (5.9 mL, 42.3 mmol), sodium triacetoxyborohydride (6.72 g, 31.7 mmol) and acetic acid (1.98 mL) and stir at room temperature for 18 hr. Add aq. saturated sodium bicarbonate and extract four times with DCM. Dry combined organic layers (magnesium sulfate), filter, concentrate, and purify (silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate:hexanes then 10:90 to 20:80 methanol:ethyl acetate) to give 3′-chloro-4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (5.2 g, 88%). MS (ES): m/z=321 [M+H]+.

Workup

  1. extractionAdd aq. saturated sodium bicarbonate and extract four times with DCM
  2. customDry
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify (silica gel chromatography
  6. washeluting with 50:50 to 100:0 ethyl acetate

Sources & evidence

ORD record
ord-8001cda7f8dd4de2aa89f2d9acdb9526
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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