Benzyl Bromide → 4-[3-(6-Benzyl-1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-2-yl)-1H-indazol-6-yl]-5-ethyl-2-fluoro-phenol

HRID 340019노트

반응식

HRID 340019 반응식
Br.Br.Br.[CH2:4]([C:6]1[C:7]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([C:23]4[NH:32][C:26]5[CH2:27][CH2:28][NH:29][CH2:30][CH2:31][C:25]=5[N:24]=4)=[N:19][NH:20]3)=[CH:16][CH:15]=2)=[CH:8][C:9]([F:13])=[C:10]([OH:12])[CH:11]=1)[CH3:5].[CH2:33](Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:33]([N:29]1[CH2:30][CH2:31][C:25]2[N:24]=[C:23]([C:18]3[C:17]4[C:21](=[CH:22][C:14]([C:7]5[C:6]([CH2:4][CH3:5])=[CH:11][C:10]([OH:12])=[C:9]([F:13])[CH:8]=5)=[CH:15][CH:16]=4)[NH:20][N:19]=3)[NH:32][C:26]=2[CH2:27][CH2:28]1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

참가 물질

5

반응물 3

HCID 7498Benzyl BromideHCID 81531DiisopropylethylamineHCID 1363339625-Ethyl-2-fluoro-4-[3-(1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-2-yl)-1H-indazol-6-yl]-phenol trihydrobromide salt

생성물 1

HCID 1362639604-[3-(6-Benzyl-1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-2-yl)-1H-indazol-6-yl]-5-ethyl-2-fluoro-phenol수율 10.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

To a solution of 5-ethyl-2-fluoro-4-[3-(1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-2-yl)-1H-indazol-6-yl]-phenol trihydrobromide salt (Preparation 32, 50 mg, 80 μmol) in DMF (1 mL), was added benzyl bromide (14.4 mg, 10 μL, 85 μmol), and DIPEA (56 μL, 320 μmol). The reaction mixture was heated at 50° C. for 18 hours. The reaction mixture was then cooled to room temperature and partitioned between EtOAc (50 mL) and water (50 mL). The organic layer was washed with brine (50 mL), dried over sodium sulfate and concentrated in vacuo to furnish a brown oil. The crude material was purified by reverse phase chromatography (Method C) to afford 4 mg of the title compound.

후처리

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. custompartitioned between EtOAc (50 mL) and water (50 mL)
  3. washThe organic layer was washed with brine (50 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto furnish a brown oil
  7. customThe crude material was purified by reverse phase chromatography (Method C)

출처 및 근거

ORD 기록
ord-15ebb58e6eec4fe4ac545024864928bd
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08895544B2

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