Potassium Carbonate → HCID 178502398、化合物

HRID 1411357ノート

反応式

HRID 1411357 の反応式
C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9](=[O:42])[NH:10][C@H:11]([C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22]1[NH:23][CH:24]=[C:25]([C:27]2[CH:32]=[CH:31][C:30](B3OC(C)(C)C(C)(C)O3)=[CH:29][CH:28]=2)[N:26]=1)=[O:16])[CH:12]([CH3:14])[CH3:13].[C:43]([O:47][C:48]([N:50]1[CH2:55][C@@H:54]([CH3:56])[N:53]([C:57]2[CH:62]=[CH:61][C:60]([C:63](=[O:78])[NH:64][C:65]3[CH:70]=[C:69]([O:71][C:72]([F:75])([F:74])[F:73])[C:68](Br)=[CH:67][C:66]=3[F:77])=[CH:59][N:58]=2)[CH2:52][C@@H:51]1[CH3:79])=[O:49])([CH3:46])([CH3:45])[CH3:44]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:43]([O:47][C:48]([N:50]1[CH2:55][C@@H:54]([CH3:56])[N:53]([C:57]2[CH:62]=[CH:61][C:60]([C:63](=[O:78])[NH:64][C:65]3[C:66]([F:77])=[CH:67][C:68]([C:30]4[CH:31]=[CH:32][C:27]([C:25]5[N:26]=[C:22]([C@@H:18]6[CH2:19][CH2:20][CH2:21][N:17]6[C:15](=[O:16])[C@@H:11]([NH:10][C:9]([O:8][CH3:7])=[O:42])[CH:12]([CH3:14])[CH3:13])[NH:23][CH:24]=5)=[CH:28][CH:29]=4)=[C:69]([O:71][C:72]([F:75])([F:74])[F:73])[CH:70]=3)=[CH:59][N:58]=2)[CH2:52][C@@H:51]1[CH3:79])=[O:49])([CH3:46])([CH3:45])[CH3:44]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 67494984(2S,5R)-4-[5-(4-bromo-2-fluoro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl esterHCID 178502353HCID 178502353、化合物

生成物 1

HCID 178502398HCID 178502398、化合物

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

Potassium carbonate (470 mg, 3.4 mmol) was added to a solution of [(S)-2-methyl-1-((S)-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (340 mg, 0.68 mmol) and (2S,5R)-4-[5-(4-bromo-2-fluoro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (400 mg, 0.68 mmol; Preparation 49) dissolved in toluene (2.5 mL) and water (0.73 mL). The reaction mixture was sparged under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (94 mg, 0.081 mmol) was added and the reaction mixture was sparged with nitrogen and heated at 100° C. for 4 h. The reaction mixture was diluted in ethyl acetate and washed with water and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated to produce (2S,5R)-4-[5-(5-fluoro-4′-{2-[(S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1H-imidazol-4-yl}-2-trifluoromethoxy-biphenyl-4-ylcarbamoyl)-pyridin-2-yl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester as a red solid.

後処理

  1. customThe reaction mixture was sparged under nitrogen
  2. customthe reaction mixture was sparged with nitrogen
  3. additionThe reaction mixture was diluted in ethyl acetate
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-e49471403de648e08bccd88a77130f81
出典データセット
uspto-grants-2014_12
特許番号
US08921372B2

反応ノート

読み込み中…