2-Bromopropane → 8-Isopropoxy-[1,6]naphthyridine-7-carboxylic acid methyl ester

HRID 640805Notes

Reaction equation

HRID 640805 reaction equation
Br[CH:2]([CH3:4])[CH3:3].[CH3:5][O:6][C:7]([C:9]1[C:18]([OH:19])=[C:17]2[C:12]([CH:13]=[CH:14][CH:15]=[N:16]2)=[CH:11][N:10]=1)=[O:8].C([O-])([O-])=O.[K+].[K+].[NH4+].[Cl-]>CS(C)=O>[CH3:5][O:6][C:7]([C:9]1[C:18]([O:19][CH:2]([CH3:4])[CH3:3])=[C:17]2[C:12]([CH:13]=[CH:14][CH:15]=[N:16]2)=[CH:11][N:10]=1)=[O:8]

Participants

6

Reactant 4

HCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 22346294Methyl 8-hydroxy-1,6-naphthyridine-7-carboxylate

Product 1

HCID 592566178-Isopropoxy-[1,6]naphthyridine-7-carboxylic acid methyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

2-Bromopropane (0.9 mL) was added to a stirred mixture of 8-hydroxy-[1,6]naphthyridine-7-carboxylic acid methyl ester (prepared according to Anthony and coworkers, Patent WO 02/30931 A2) (1.00 g, 4.90 mmol), K2CO3 (2.79 g) and DMSO (15 mL). After 40 h at 50° C., sat'd NH4Cl (20 mL) was added and the mixture extracted with dichloromethane (10 mL×3). The extracts were combined and concentrated. Diethyl ether (40 mL) was added to the residue and the resulting mixture washed successively with H2O (5 mL×2) and brine (10 mL), and dried. Solvent removal gave 8-isopropoxy-[1,6]naphthyridine-7-carboxylic acid methyl ester (1.06 g, 88%).—1H NMR (CDCl3): δ 9.16 (dd, J=1.9 and 4.3, 1H), 9.03 (s, 1H), 8.34 (dd, J=1.9 and 8.5, 1 H), 7.63 (dd, J=4.3 and 8.5, 1H), 5.33 (sep, J=6.2, 1H), 4.04 (s, 3H), 1.42 (d, J=6.2, 6H).

Workup

  1. extractionthe mixture extracted with dichloromethane (10 mL×3)
  2. concentrationconcentrated
  3. additionDiethyl ether (40 mL) was added to the residue
  4. washthe resulting mixture washed successively with H2O (5 mL×2) and brine (10 mL)
  5. customdried
  6. customSolvent removal

Sources & evidence

ORD record
ord-4f5c88f305be49149226fc14d5bdb8f6
Source dataset
uspto-grants-2010_04
Patent number
US07692011B2

Reaction notes

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