Potassium Carbonate → (3S)-4-((6-(2-bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)-2,2-dimethylmorpholine-3-carboxylic acid

HRID 524618Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:13]([CH2:20]Br)[NH:12][C:11]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)=[N:10]1.[CH3:27][C:28]1([CH3:37])[O:33][CH2:32][CH2:31][NH:30][C@@H:29]1[C:34]([OH:36])=[O:35].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[N:10]=[C:11]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[NH:12][C:13]([CH2:20][N:30]2[CH2:31][CH2:32][O:33][C:28]([CH3:27])([CH3:37])[C@H:29]2[C:34]([OH:36])=[O:35])=[C:14]1[C:15]([O:17][CH2:18][CH3:19])=[O:16]

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (7.7 g, 15.3 mmol), (S)-2,2-dimethylmorpholine-3-carboxylic acid (2.44 g, 15.3 mmol) and potassium carbonate (4.23 g, 30.6 mmol) in anhydrous ethanol (154 mL) was stirred at 25° C. for 16 hours. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/MeOH (V/V)=25/1) to give the title compound as a yellow solid (5.8 g, 65%). The compound was characterized by the following spectroscopic data:

Workup

filtrationThe reaction mixture was filtered
concentrationthe filtrate was concentrated in vacuo
customThe residue was purified by a silica gel column chromatography (DCM/MeOH (V/V)=25/1)

Sources & evidence

ORD record: ord-f5e9e9c1816f4f45bf89227f2421f58b
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340538B2

Reaction notes

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