Quinoline → Propylamine

HRID 456577Notes

Reaction equation

HRID 456577 reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]=[CH:4][CH:3]=1.CS(Cl)(=O)=O.[N:17]1C2C(=CC=CC=2)[CH:20]=[CH:19][CH:18]=1>P(Cl)(Cl)(Cl)=O.N1C=CC=CC=1>[NH2:17][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]=[CH:4][CH:3]=1.[CH2:18]([NH2:17])[CH2:19][CH3:20]

Participants

7

Reactant 3

HCID 7047QuinolineHCID 31297Methanesulfonyl chlorideHCID 178516432HCID 178516432, compound

Product 2

HCID 7852PropylamineHCID 5893541,5-Naphthyridin-4-amine

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 24813Phosphorus oxychlorideSolvent

Procedure

4-Hydroxy-1,5-naphthyridines can be prepared from 3-aminopyridine derivatives by reaction with diethyl ethoxymethylene malonate to produce the 4-hydroxy-3-carboxylic acid ester derivative with subsequent hydrolysis to the acid, followed by thermal decarboxylation in quinoline (as for example described for 4-Hydroxy-[1,5]naphthyridine-3-carboxylic acid, 3. T. Adams et al., J.Amer.Chem.Soc., 1946, 68, 1317). A 4-hydroxy-[1,5]naphthyridine can be converted to the 4-chloro derivative by heating in phosphorus oxychloride, or to the 4-methanesulphonyloxy or 4-trifluoromethanesulphonyloxy derivative by reaction with methanesulphonyl chloride or trriluoromethanesulphonic anhydride, respectively, in the presence of an organic base. A 4-amino 1,5-naphthyridine can be obtained from the 4-chloro, 4-methanesulphonyloxy or 4-trifluoromethanesulphonyloxy derivative by reaction with n-propylamine in pyridine.

Workup

  1. customwith subsequent hydrolysis to the acid

Sources & evidence

ORD record
ord-a4e6f57128ae492bb8c677060bb86db6
Source dataset
uspto-grants-2007_03
Patent number
US07186730B2

Reaction notes

Loading…