2-Methylpyrrolidine → 1-[2-(6-Bromo-naphthalen-2-yl)-ethyl]-2-methyl-pyrrolidine

HRID 857531Notes

Reaction equation

HRID 857531 reaction equation
[O-]S(C(F)(F)F)(=O)=O.BrC1C=C2C(=CC=1)C=C(O)C=C2.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.BrC1C=C2C(=CC=1)C=C(OS(C(F)(F)F)(=O)=O)C=C2.[Br:55][C:56]1[CH:65]=[CH:64][C:63]2[C:58](=[CH:59][CH:60]=[C:61]([CH:66]=[CH2:67])[CH:62]=2)[CH:57]=1.[CH3:68][CH:69]1[CH2:73][CH2:72][CH2:71][NH:70]1.C([Li])CCC>[Pd]>[Br:55][C:56]1[CH:57]=[C:58]2[C:63](=[CH:64][CH:65]=1)[CH:62]=[C:61]([CH2:66][CH2:67][N:70]1[CH2:71][CH2:72][CH2:73][CH:69]1[CH3:68])[CH:60]=[CH:59]2

Participants

9

Reactant 7

HCID 130032-MethylpyrrolidineHCID 271446-Bromo-2-naphthalenolHCID 67749Trifluoromethanesulfonic anhydrideHCID 2758875TrifluoromethanesulfonateHCID 115648892-Bromo-6-ethenylnaphthalene2×HCID 153112166-Bromo-2-naphthyl TrifluoromethanesulfonateHCID 178418339Butyllithium

Product 1

HCID 115225881-[2-(6-Bromo-naphthalen-2-yl)-ethyl]-2-methyl-pyrrolidine

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

One process for the preparation of 2-{6-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-naphthalen-2-yl}-2H-pyridazin-3-one, which demonstrates activity as a histamine-3 receptor ligand, involves treating an inexpensive and readily available starting material, 6-bromo-naphthalen-2-ol, to afford 2-{6-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-naphthalen-2-yl}-2H-pyridazin-3-one. Briefly, the process involves providing 6-bromo-naphthalen-2-ol. Preparing the triflate, or trifluoromethansulfonic acid ester, of 6-bromo-naphthalen-2-ol (2) with trifluoromethanesulfonic anhydride or another suitable trifluoromethanesulfonic reagent. The resulting trifluoro-methanesulfonic acid 6-bromo-naphthalen-2-yl ester (2) is converted to 2-bromo-6-vinyl-naphthalene (3) via a Pd-catalyzed Suzuki cross-coupling reaction. The 2-bromo-6-vinyl-naphthalene is reacted with a 2-methylpyrrolidine anion generated with n-butyllithium to provide 1-[2-(6-bromo-naphthalen-2-yl)-ethyl]-2-methyl-pyrrolidine (4). Compound (4) is reacted with 2H-pyridazin-3-one to provide the desired 2-{6-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-naphthalen-2-yl}-2H-pyridazin-3-one (5).

Workup

  1. customreaction

Sources & evidence

ORD record
ord-97fd7cc8812c450087c1f0208b45381c
Source dataset
uspto-grants-2006_12
Patent number
US07145005B2

Reaction notes

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