1H-Pyrrole-2-carboxylic acid, 1-amino-3-bromo-, methyl ester synthesis

Yield:1403942-81-3 85%

Reaction Conditions:

Stage #1: methyl 3-bromo-1H-pyrrole-2-carboxylatewith sodium hydride in N,N-dimethyl-formamide at 0; for 0.333333 h;
Stage #2: with O-(diphenylphosphinyl)hydroxylamine in N,N-dimethyl-formamide at 0 - 20; for 2 h;

Steps:

1 Example 1 2-(4-amino-3-methyl-2-oxa-8-aza-spiro[4.5]dec-8-yl)-5-(2,3-dichloro-phenyl)-3-methyl-3H-pyrrole[2,1f][1,2,4]triazin-4-one (compound 1)

3-Bromo-1H-pyrrole-2-carboxylic acid methyl ester(20.3g, 100mmol) dissolved in 100mL DMF, cooled to 0°C, then added NaH (4.9g, 130mmol) in small amounts several times, stirred for 20min, and added O-diphenylphosphohydroxylamine (23.0g, 120mmol) in batches , Raise to room temperature and react for 2 hours. Add 100mL of water, extract twice with ethyl acetate, combine the organic phases, then wash once with water, once with saturated brine, dry, and separate and purify by column chromatography to obtain intermediate 1.1 17.0g, with a yield of 85.0%.

References:

CN111393459,2020,A Location in patent:Paragraph 0021-0023