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 1894330ノート

反応式

HRID 1894330 の反応式
[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]

参加物

9

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
180 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-92a23d3464544427858447a41b1d9560
出典データセット
uspto-grants-2013_08
特許番号
US08513239B2

反応ノート

読み込み中…