Citric Acid → Ethanesulfonic acid {6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-p-tolyl-pyrimidin-4-yl}-amide

HRID 2252722Notes

Reaction equation

[OH:1][CH2:2][CH2:3][O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])[C:6]=1[C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1.[H-].[Na+].Cl[C:27]1[N:32]=[CH:31][C:30]([Br:33])=[CH:29][N:28]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[Br:33][C:30]1[CH:29]=[N:28][C:27]([O:1][CH2:2][CH2:3][O:4][C:5]2[N:10]=[CH:9][N:8]=[C:7]([NH:11][S:12]([CH2:15][CH3:16])(=[O:13])=[O:14])[C:6]=2[C:17]2[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=2)=[N:32][CH:31]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Ethanesulfonic acid [6-(2-hydroxy-ethoxy)-5-p-tolyl-pyrimidin-4-yl]-amide (135 mg) was dissolved in THF (15 ml) and sodium hydride (80 mg) was added followed by stirring for 15 min at 50° C. Then 2-chloro-5-bromo-pyrimidine (162 mg) was added and stirring was continued for 8 h at 70 C. The reaction mixture was poured onto ice water, acidified with solid citric acid and extracted with ethylacetate. The combined organic extracts were dried over magnesium sulfate and the solvent was evaporated. The crude material was purified by plate chromatography with ethyl acetate/hexane=½ to give ethanesulfonic acid {6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-p-tolyl-pyrimidin-4-yl}-amide (68 mg) as a white powder. LC-MS: tR: 4.64, [M+H]+: 496.19.

Workup

stirringstirring
waitwas continued for 8 h at 70 C
additionThe reaction mixture was poured onto ice water
extractionextracted with ethylacetate
dry with materialThe combined organic extracts were dried over magnesium sulfate
customthe solvent was evaporated
customThe crude material was purified by plate chromatography with ethyl acetate/hexane=½

Sources & evidence

ORD record: ord-655d6fd4792649d384053cec1d355535
Source dataset: uspto-grants-2008_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07323465B2

Reaction notes

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