Methanesulfonyl chloride → rac-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-{4-[2-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-piperazin-1-yl}-methanone

HRID 1894330Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1894330
[C:1]([C:5]1[N:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8]([C:14]2[N:15]([C:35]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[O:36])[C:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)([CH3:27])[C:17]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)([CH3:19])[N:18]=2)=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:43][C:44]1([CH3:56])[O:48][C@H:47]([CH2:49][CH2:50]OS(C)(=O)=O)[CH2:46][O:45]1.CC1(C)O[C@H](CCO)CO1.CS(Cl)(=O)=O.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C.C(N(CC)CC)C>[C:1]([C:5]1[N:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8]([C:14]2[N:15]([C:35]([N:37]3[CH2:42][CH2:41][N:40]([CH2:50][CH2:49][C@@H:47]4[CH2:46][O:45][C:44]([CH3:56])([CH3:43])[O:48]4)[CH2:39][CH2:38]3)=[O:36])[C@@:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)([CH3:27])[C@@:17]([C:20]3[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=3)([CH3:19])[N:18]=2)=[CH:7][N:6]=1)([CH3:2])([CH3:3])[CH3:4]

Komponenten

9

Edukt 5

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 11480522(4R)-4-(2-Hydroxyethyl)-2,2-dimethyl-1,3-dioxolaneHCID 67205751[2-(2-tert-Butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanoneHCID 86615867methanesulfonic acid 2-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl ester

Produkt 1

HCID 68942827rac-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-{4-[2-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-piperazin-1-yl}-methanone

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8471TriethylamineLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
180 °C

Versuchsvorschrift

The mixture of [2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (80 mg, 0.13 mmol), methanesulfonic acid 2-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl ester (437 mg, 1.95 mmol, prepared from 2-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethanol and methanesulfonyl chloride in the present of triethylamine) and diisopropylethylamine (110 uL, 0.65 mmol) in dry dimethylformamide (3 mL) was heated in the microwave at 180° C. for 20 min. Upon cooling to room temperature, the reaction mixture was diluted with ethyl acetate and washed with water (5×) and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification of the crude residue by flash column chromatography (silica gel, eluting with ethyl acetate and hexane) gave rac-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-{4-[2-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-piperazin-1-yl}-methanone (45 mg).

Aufarbeitung

  1. temperatureUpon cooling to room temperature
  2. washwashed with water (5×) and brine
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customPurification of the crude residue
  6. washby flash column chromatography (silica gel, eluting with ethyl acetate and hexane)

Quellen und Nachweise

ORD-Eintrag
ord-92a23d3464544427858447a41b1d9560
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08513239B2

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