2-Oxazolidinone → HCID 59410143, compound

HRID 2405005Notes

Reaction equation

HRID 2405005 reaction equation
O1CCNC1=O.[NH2:7][CH2:8][C@@H:9]1[O:13][C:12](=[O:14])[N:11]([C:15]2[CH:20]=[C:19]([CH3:21])[C:18]([N:22]3[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][CH2:29][O:30][Si:31]([C:44]([CH3:47])([CH3:46])[CH3:45])([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[C:23]3=[O:48])=[C:17]([CH3:49])[CH:16]=2)[CH2:10]1.[Cl:50][C:51]1[S:55][C:54]([C:56](Cl)=[O:57])=[CH:53][CH:52]=1>>[C:44]([Si:31]([C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[O:30][CH2:29][CH2:28][C:24]1[C:23](=[O:48])[N:22]([C:18]2[C:17]([CH3:49])=[CH:16][C:15]([N:11]3[CH2:10][C@H:9]([CH2:8][NH:7][C:56]([C:54]4[S:55][C:51]([Cl:50])=[CH:52][CH:53]=4)=[O:57])[O:13][C:12]3=[O:14])=[CH:20][C:19]=2[CH3:21])[CH:27]=[CH:26][CH:25]=1)([CH3:45])([CH3:46])[CH3:47]

Participants

4

Reactant 3

HCID 739492-OxazolidinoneHCID 5892235-Chlorothiophene-2-carbonyl ChlorideHCID 59410159HCID 59410159, compound

Product 1

HCID 59410143HCID 59410143, compound

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).

Workup

  1. customproduces

Sources & evidence

ORD record
ord-72091078f9894e18813cef3fff68f242
Source dataset
uspto-grants-2014_08
Patent number
US08802860B2

Reaction notes

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