Chemical Properties
white to light yellow crystal powder
Uses
2-Amino-5-methoxybenzoic acid is a general reagent used in the synthesis of substituted isoquinolinonaphthyridines, quinazolinones, imidazobenzodiazepines, pyridoquinazolones and polycyclic hexahydrobenzo[
c]acridines.
Uses
2-Amino-5-methoxybenzoic Acid is used in the synthesis of quinazolinone class of histamine H3 receptor inverse agonists. It is also used in the synthesis of Alogliptin, a selective inhibitor of the s
erine protease dipeptidyl peptidase IV.
Definition
ChEBI: 2-Amino-5-methoxybenzoic acid is a methoxybenzoic acid.
reaction suitability
reaction type: solution phase peptide synthesis
Synthesis
Using 5-methoxy-2-nitrobenzoic acid (1) as starting material, its nitro group was reduced by catalytic hydrogenation using H2 and Pd/C to afford 2-amino-5-methoxybenzoic acid (2) in quantitative yield. Subsequently, compound (2) was subjected to diazotization reaction with NaNO2 followed by treatment with Na2S2 to obtain stable disulfide compound (3) in 80% yield. This disulfide (3) was directly reacted with SOCl2 without further purification, followed by reaction with 2-chloroethylamine in the presence of Et3N to produce amide (4) in 90% yield. The compound (4) was converted to the cyclized product (5) by a one-pot method with trimethylphosphine and Et3N co-refluxed in THF. Finally, reduction of the cyclized amide (5) using LiAlH4 afforded 7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine (6).
References
[1] Patent: US2007/49572, 2007, A1. Location in patent: Page/Page column 34
[2] Patent: US2005/215540, 2005, A1. Location in patent: Page/Page column 37
[3] Patent: WO2016/23826, 2016, A1. Location in patent: Page/Page column 40
[4] Synthesis (Germany), 2017, vol. 49, # 1, p. 135 - 144
[5] Medicinal Chemistry Research, 2002, vol. 11, # 9, p. 504 - 537
