tert-Butyldiphenylchlorosilane → 3-(2-{[tert-Butyl(diphenyl)silyl]oxy}ethyl)-1-(2,6-dimethyl-4-nitrophenyl)pyridin-2(1H)-one

HRID 2405004Notes

Reaction equation

HRID 2405004 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([CH3:11])[C:3]=1[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][CH2:19][OH:20])[C:13]1=[O:21].[C:22]([Si:26](Cl)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([CH3:25])([CH3:24])[CH3:23]>>[Si:26]([O:20][CH2:19][CH2:18][C:14]1[C:13](=[O:21])[N:12]([C:3]2[C:2]([CH3:1])=[CH:7][C:6]([N+:8]([O-:10])=[O:9])=[CH:5][C:4]=2[CH3:11])[CH:17]=[CH:16][CH:15]=1)([C:22]([CH3:25])([CH3:24])[CH3:23])([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

3

Reactant 2

HCID 94078tert-ButyldiphenylchlorosilaneHCID 545754381-(2,6-Dimethyl-4-nitrophenyl)-3-(2-hydroxyethyl)pyridin-2(1H)-one

Product 1

HCID 594101853-(2-{[tert-Butyl(diphenyl)silyl]oxy}ethyl)-1-(2,6-dimethyl-4-nitrophenyl)pyridin-2(1H)-one

Procedure

To prepare the compound of the Formula (Ia), 3-bromopyridin-2(1H)-one (III) is reacted with 1-fluoro-2,5-dimethyl-4-nitrobenzene (IV) to give 3-bromo-1-(2,6-dimethyl-4-nitrophenyl)pyridin-2(1H)-one (V). Then, (V) is converted with tributylvinyl tin and tetrakis(triphenylphosphine)palladium into 1-(2,6-dimethyl-4-nitrophenyl)-3-vinylpyridin-2(1H)-one (VI). Hydroboration and oxidation of (VI) produces 1-(2,6-dimethyl-4-nitrophenyl)-3-(2-hydroxyethyl)pyridin-2(1H)-one (VII). In order to protect the hydroxy group, (VII) is reacted with tert-butyl(chloro)diphenylsilane in the presence of a base, giving 3-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-1-(2,6-dimethyl-4-nitrophenyl)pyridin-2(1H)-one (VIII). The reduction of the nitro group in (VIII) leads to 1-(4-amino-2,6-dimethylphenyl)-3-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)pyridin-2(1H)-one (IX). Then follows the reaction of (IX) with (S)-epoxyphthalimide (X) to give 2-[(2R)-3-({4-[3-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-2-oxopyridin-1(2H)-yl]-3,5-dimethylphenyl}amino)-2-hydroxypropyl]-1H-isoindole-1,3(2H)-dione (XI). Ring closure to the oxazolidinone and cleaving off the phthalimide group produces starting from (XI) 1-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2,6-dimethylphenyl}-3-(2-{[tert-butyl-(diphenyl)silyl]oxy}ethyl)pyridin-2(1H)-one (XII), which is reacted with 5-chlorothiophene-2-carbonyl chloride (XIII) to give N-[((5S)-3-{4-[3-(2-{[tert-butyl-(diphenyl)silyl]oxy}ethyl)-2-oxopyridin-1(2H)-yl]-3,5-dimethylphenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]-5-chlorothiophene-2-carboxamide (XIV). Cleaving off the protective group in (XIV) produces 5-chloro-N-[((5S)-3-{4-[3-(2-hydroxyethyl)-2-oxopyridin-1(2H)-yl]-3,5-dimethylphenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]thiophene-2-carboxamide (IIa), which is reacted with trans-4-aminohexanol (XV) to give 5-chloro-N-{[(5S)-3-{4-[3-{2-[(trans-4-hydroxycyclohexyl)amino]ethyl}-2-oxopyridin-1(2H)-yl]-3,5-dimethylphenyl}-2-oxo-1,3-oxazolidin-5-yl]methyl}thiophene-2-carboxamide (Ia).

Sources & evidence

ORD record
ord-ced0af0b287946db9892b1e1d1a0e7f2
Source dataset
uspto-grants-2014_08
Patent number
US08802860B2

Reaction notes

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