Hydrazine → 3-Benzyl-8-chloro[1,2,4]triazolo[4,3-a]pyrazine

HRID 2371692Notes

Reaction equation

HRID 2371692 reaction equation
N1C=CNC(=O)C1=O.ClC1C(Cl)=NC=CN=1.NN.[Cl:19][C:20]1[C:25]([NH:26][NH2:27])=[N:24][CH:23]=[CH:22][N:21]=1.F[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH2:35][C:36](OCC)(OCC)OCC>C1(C)C(C)=CC=CC=1>[Cl:19][C:20]1[C:25]([NH:26][NH2:27])=[N:24][CH:23]=[CH:22][N:21]=1.[CH2:35]([C:36]1[N:24]2[CH:23]=[CH:22][N:21]=[C:20]([Cl:19])[C:25]2=[N:26][N:27]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:29]=1

Participants

8

Reactant 5

HCID 9321HydrazineHCID 785752,3-DichloropyrazineHCID 3214302-Chloro-3-hydrazinopyrazineHCID 2774693Pyrazine-2,3-diolHCID 10355054HCID 10355054, compound

Product 2

HCID 3214302-Chloro-3-hydrazinopyrazineHCID 102435763-Benzyl-8-chloro[1,2,4]triazolo[4,3-a]pyrazineYield 96%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

2-Chloro-3-hydrazinopyrazine was prepared in four steps. The procedure of J. Adachi and N. Sato, J.Org.Chem. 37, 221 (1972) was used to prepare 2,3(1H,4H)-pyrazinedione in two steps, followed by chlorination and reaction of the dichloropyrazine with hydrazine as described in S. W. Schneller and J. L. May, J.Het.Chem. 15,987 (1978). A mixture of 2-chloro-3-hydrazinopyrazine (8.51 g, 58.9 mmol), 1-fluoro-2-(2,2,2-triethoxyethyl)benzene from 1(A) (34.7 g, 135 mmol) and xylene (125 mL) (dried over calcium chloride) was refluxed for 3 hours. The solvent was removed by spin evaporation in vacuo. The solid residue was triturated in ether (200 mL) and the solid was collected by suction filtration. The solid was rinsed with ether and dried with aspirator suction to give 14.9 g (96%) of crude 3-benzyl-8-chloro-1,2,4-triazolo[4,3-a]pyrazine. Recrystallisation of 1.0 g of crude 3-benzyl-8-chloro-1,2,4-triazolo[4,3-a]pyrazine from ethanol:water gave 0.697 g of the analytically pure product, mp. 126°-127° C.; UV (0.1 N hydrochloride acid+10% ethanol): λmax 300 nm (ε4200); (pH 7.0 buffer+10% ethanol): λmax 300 nm (ε4300); nmr(DMSO-d6) δ8.58 (d, 1H, J=4.7 Hz, H-5 or H-6), 7.79 (d, 1H, J=4.7 Hz, H-5 or H-6), 7.09-7.40 (complex multiplets, 4H, ArH), 4.60 (s, 2H, CH2); ms: m/e 262 (M+), 261 (M-1+), 243 (M-F+), 227 (M-Cl+), 109 (C7H6F+).

Workup

  1. temperaturewas refluxed for 3 hours
  2. customThe solvent was removed by spin evaporation in vacuo
  3. customThe solid residue was triturated in ether (200 mL)
  4. filtrationthe solid was collected by suction filtration
  5. washThe solid was rinsed with ether
  6. customdried with aspirator suction

Sources & evidence

ORD record
ord-fb575ea8f35a460d9b683c48b74ca184
Source dataset
uspto-grants-1992_03
Patent number
US05095018

Reaction notes

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