Isonitrosoacetophenone → 2-Amino-3-benzyl-5-phenylpyrazine

HRID 2407194Notes

Reaction equation

[CH:1]1[CH:6]=[CH:5][C:4]([C:7](/[CH:9]=[N:10]/O)=O)=[CH:3][CH:2]=1.Cl.[NH2:13][CH:14]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:15]#[N:16]>Cl[Ti](Cl)(Cl)Cl.N1C=CC=CC=1>[NH2:16][C:15]1[C:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:13][C:7]([C:4]2[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=2)=[CH:9][N:10]=1

Participants

Conditions

Temperature: -20 °C

Procedure

A round bottomed flask was charged with 5 g (33.5 mmol) of 2-isonitrosoacetophenone, 6.7 g (36.8 mmol) of 2-amino-3-phenylpropanenitrile hydrochloride and 100 mL of dry pyridine. The mixture was cooled to −20° C. and 4.6 mL (40.0 mmol) of TiCl4 was added dropwise. The reaction was kept at −20° C. for 30 min and heated to 80° C. for 2.5 hrs. The solvent was evaporated, and the residue taken up in 1 L of DCM. This solution was washed with saturated NaHCO3 and brine. All volatiles were evaporated, and the residue redissolved in ethanol (400 mL). Raney Ni (2.0 g, aqueous suspension) was added, and the reaction allowed to stir for 5 days under 1 atm of hydrogen. The mixture was passed through celite, and volatiles removed. The residue was chromatographed on silica gel (heptanes/DCM) to give 2.5 g (29%) of 2-amino-3-benzyl-5-phenylpyrazine.

Workup

temperatureheated to 80° C. for 2.5 hrs
customThe solvent was evaporated
washThis solution was washed with saturated NaHCO3 and brine
customAll volatiles were evaporated
dissolutionthe residue redissolved in ethanol (400 mL)
additionRaney Ni (2.0 g, aqueous suspension) was added
customremoved
customThe residue was chromatographed on silica gel (heptanes/DCM)

Sources & evidence

ORD record: ord-8323f4cf4e1e4038a7a55b31ef4aea03
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809529B2

Reaction notes

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