Diisopropylethylamine → Ethyl 4-(2-bromo-4-fluorophenyl)-6-(((S)-3-(hydroxycarbamoyl)morpholino)methyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate

温度

25 °C

A solution of (3S)-4-(((6-(2-bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholine-3-carboxylic acid (0.74 g, 1.36 mmol), EDC.HCl (0.31 g, 1.62 mmol), HOAt (185 mg, 1.36 mmol) and DIPEA (210 mg, 1.62 mmol) in DCM (20 mL) was stirred at −10° C. for 30 minutes. Then to the mixture was added a solution of O-(tert-butyldimethylsilyl)hydroxylamine (0.2 g, 1.36 mmol) in DCM (2.0 mL) slowly at −10° C. Then the mixture was warmed to 25° C. and stirred for 12 hours. The mixture was concentrated in vacuo and the residue was dissolved in a solution of HCl in EtOAc (6 mol/L, 10 mL), then the mixture was stirred at 25° C. for 2 hours. The reaction mixture was diluted with EtOAc (200 mL) and water (100 mL), and the mixture was adjusted to pH 7 with aqueous ammonia. The organic layer was dried over Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/MeOH (V/V)=30/1) to give the title compound as a yellow solid (0.05 g, 6.5%). The compound was characterized by the following spectroscopic data:

1. concentrationThe mixture was concentrated in vacuo
2. dissolutionthe residue was dissolved in a solution of HCl in EtOAc (6 mol/L, 10 mL)
3. stirringthe mixture was stirred at 25° C. for 2 hours
4. additionThe reaction mixture was diluted with EtOAc (200 mL) and water (100 mL)
5. dry with materialThe organic layer was dried over Na2SO4
6. concentrationconcentrated in vacuo
7. customThe residue was purified by a silica gel column chromatography (DCM/MeOH (V/V)=30/1)

ORDレコード

ord-13d8c898558848618ae2482ee8e3219a

出典データセット

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09340538B2