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

HRID 220555Notes

Reaction equation

HRID 220555 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.[CH2:16]([N:18]1[CH:22]=[C:21]([CH:23]=O)[C:20]([CH3:25])=[N:19]1)[CH3:17].C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(=O)(O)[O-].[Na+].C(O)(=O)C>[Cl:3][C:4]1[C:5]([N:10]2[CH2:11][CH2:12][N:13]([CH2:23][C:21]3[C:20]([CH3:25])=[N:19][N:18]([CH2:16][CH3:17])[CH:22]=3)[CH2:14][CH2:15]2)=[N:6][CH:7]=[CH:8][N:9]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 5732031-ethyl-3-methyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 866416583'-chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

Product 1

HCID 866416653'-chloro-4-(1-ethyl-3-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinylYield 65%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 63651,1-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Combine 3′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (2.21 g, 8.18 mmol), 1-ethyl-3-methyl-1H-pyrazole-4-carbaldehyde (1.3 g, 9.40 mmol) and triethylamine (1.31 mL, 9.40 mmol) in dichloroethane (50 mL). Add glacial acetic acid (0.85 mL) followed by sodium triacetoxyborohydride (2.99 g, 14.1 mmol). Stir at room temperature for 20 hr. Dilute with saturated aq. sodium bicarbonate then extract three times using DCM. Dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 4.5:95.5 methanol (with 2 M ammonia):DCM), to give 3′-chloro-4-(1-ethyl-3-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl as a yellow oil (1.702 g, 65%). MS (ES): m/z=321 [M+H]+.

Workup

  1. extractionthen extract three times
  2. dry with materialDry (sodium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 4.5:95.5 methanol (with 2 M ammonia):DCM)

Sources & evidence

ORD record
ord-442138f678e14c09b20cd62562e58b2f
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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