Water → HCID 178502447、化合物

HRID 1504341ノート

反応式

HRID 1504341 の反応式
[CH3:1][O:2][C:3](=[O:37])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][C@@H:14]([CH3:16])[CH2:13][C@H:12]1[C:17]1[NH:18][CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][C:25](B3OC(C)(C)C(C)(C)O3)=[CH:24][CH:23]=2)[N:21]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][N:48]([C:51]2[CH:56]=[CH:55][C:54]([C:57](=[O:72])[NH:58][C:59]3[CH:64]=[C:63]([O:65][C:66]([F:69])([F:68])[F:67])[C:62](Br)=[CH:61][C:60]=3[F:71])=[CH:53][N:52]=2)[C@H:47]([CH3:73])[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39].O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][N:48]([C:51]2[CH:56]=[CH:55][C:54]([C:57](=[O:72])[NH:58][C:59]3[C:60]([F:71])=[CH:61][C:62]([C:25]4[CH:26]=[CH:27][C:22]([C:20]5[N:21]=[C:17]([C@@H:12]6[CH2:13][C@H:14]([CH3:16])[CH2:15][N:11]6[C:9](=[O:10])[C@@H:5]([NH:4][C:3]([O:2][CH3:1])=[O:37])[CH:6]([CH3:8])[CH3:7])[NH:18][CH:19]=5)=[CH:23][CH:24]=4)=[C:63]([O:65][C:66]([F:69])([F:68])[F:67])[CH:64]=3)=[CH:53][N:52]=2)[C@H:47]([CH3:73])[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39]

参加物

6

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 86682814(R)-4-[5-(4-bromo-2-fluoro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl esterHCID 178502436HCID 178502436、化合物

生成物 1

HCID 178502447HCID 178502447、化合物収率 78.1%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
90 °C

実験手順

To a solution of [(S)-2-methyl-1-((2S,4S)-4-methyl-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 (170 mg, 0.33 mmol) and (R)-4-[5-(4-bromo-2-fluoro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (192 mg, 0.33 mmol, Preparation 24) dissolved in toluene (2.1 mL) and water (0.8 mL) was added potassium carbonate (230 mg, 1.67 mmol). The reaction mixture was sparged with nitrogen, Pd(dppf)Cl2CH2Cl2 (25 mg, 0.03 mmol) was added and the reaction mixture was sparged with nitrogen and heated at 90° C. overnight. The reaction mixture was cooled to RT, filtered through a pad of Celite® and silica gel and washed with EtOAc. The filtrate was washed with water and brine to produce a brownish colored oil. The residue was purified by silica gel chromatography (24 g, 40% to 100% EtOAc/hexanes) to produce the title intermediate as a yellowish solid (227 mg, 78% yield). (m/z): [M+H]+ calcd for C44H52F4N8O7 881.39. found 881.4.

後処理

  1. additionwas added
  2. customthe reaction mixture was sparged with nitrogen
  3. temperatureThe reaction mixture was cooled to RT
  4. filtrationfiltered through a pad of Celite® and silica gel
  5. washwashed with EtOAc
  6. washThe filtrate was washed with water and brine
  7. customto produce a brownish colored oil
  8. customThe residue was purified by silica gel chromatography (24 g, 40% to 100% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-799c4df83df4480e9fbcf082f2065877
出典データセット
uspto-grants-2015_12
特許番号
US09212168B2

反応ノート

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