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 340019Notes

Reaction equation

HRID 340019 reaction equation
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

Participants

5

Reactant 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

Product 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-phenolYield 10.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-15ebb58e6eec4fe4ac545024864928bd
Source dataset
uspto-grants-2014_11
Patent number
US08895544B2

Reaction notes

Loading…