3-Isocyanato-1lambda6-thiolane-1,1-dione → 1-{1-[(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-3-(1,1-dioxo-tetrahydro-1lambda6-thiophen-3-yl)-urea

HRID 1894569Notes

Reaction equation

HRID 1894569 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([N:10]2[C@@:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)([CH3:15])[C@@:13]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)([CH3:23])[N:12]=[C:11]2[C:31]2[CH:32]=[N:33][C:34]([C:40]([CH3:43])([CH3:42])[CH3:41])=[CH:35][C:36]=2[O:37][CH2:38][CH3:39])=[O:9])[CH2:4][CH2:3]1.[N:44]([CH:47]1[CH2:51][CH2:50][S:49](=[O:53])(=[O:52])[CH2:48]1)=[C:45]=[O:46]>>[C:40]([C:34]1[N:33]=[CH:32][C:31]([C:11]2[N:10]([C:8]([N:5]3[CH2:4][CH2:3][CH:2]([NH:1][C:45]([NH:44][CH:47]4[CH2:51][CH2:50][S:49](=[O:53])(=[O:52])[CH2:48]4)=[O:46])[CH2:7][CH2:6]3)=[O:9])[C@@:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)([CH3:15])[C@@:13]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)([CH3:23])[N:12]=2)=[C:36]([O:37][CH2:38][CH3:39])[CH:35]=1)([CH3:42])([CH3:41])[CH3:43]

Participants

3

Reactant 2

HCID 27722223-Isocyanato-1lambda6-thiolane-1,1-dioneHCID 57669927(4-amino-piperidin-1-yl)-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-methanone

Product 1

HCID 576699001-{1-[(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-3-(1,1-dioxo-tetrahydro-1lambda6-thiophen-3-yl)-urea

Procedure

In a manner similar to the method described in example 160, (4-amino-piperidin-1-yl)-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-methanone (example 204) was reacted with 3-isocyanato-tetrahydro-thiophene 1,1-dioxide (Chembridge) to give a mixture of diasteremers. The diastereomers were separated by supercritical fluid chromatography (Berger Instrument Multi-Gram II, Whelk-O column, eluting with 40% isopropanol in carbon dioxide) to give the title compound as post-peak. HR-MS (ES, m/z) calculated for C39H49Cl2N6O5 [(M+H)+] 783.2857, observed 783.2857.

Workup

  1. customto give
  2. additiona mixture of diasteremers
  3. customThe diastereomers were separated by supercritical fluid chromatography (Berger Instrument Multi-Gram II, Whelk-O column, eluting with 40% isopropanol in carbon dioxide)

Sources & evidence

ORD record
ord-0fdc6b1326fe486aa47f6224ff31af2f
Source dataset
uspto-grants-2013_08
Patent number
US08513239B2

Reaction notes

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