(1-Bromoethyl)benzene → HCID 25057384, compound

HRID 2387485Notes

Reaction equation

HRID 2387485 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH2:17][CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[N:12]=[CH:11]3)[C:4](=[O:24])[CH:3]=1.Br[CH:26]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:27]>CN(C=O)C>[C:28]1([CH:26]([O:1][C:2]2[CH:7]=[CH:6][N:5]([C:8]3[CH:9]=[C:10]4[C:14](=[CH:15][CH:16]=3)[N:13]([CH2:17][CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[N:12]=[CH:11]4)[C:4](=[O:24])[CH:3]=2)[CH3:27])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

4

Reactant 2

HCID 11454(1-Bromoethyl)benzeneHCID 57625508HCID 57625508, compound

Product 1

HCID 25057384HCID 25057384, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-hydroxy-1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)pyridin-2(1H)-one (84 mg, 0.26 mmol) in DMF was added Ag2O (120 mg, 0.52 mmol) followed by 1-bromoethylbenzene (71 uL, 0.52 mmol). The reaction mixture was heated to 80° C. for 4 hours, cooled to room temperature and stirred at room temperature for overnight. The reaction mixture was filtered through a thin layer of Celite, washed with CH2Cl2, and the filtrate was concentrated. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 90:10) gave 4-(1-phenylethoxy)-1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)pyridin-2(1H)-one (44 mg, 40%) as an oil. In accordance with the procedure of Example 1, the HCl salt was made to give the title compound as a white foam: 1H NMR (500 MHz, DMSO-d6) δ 9.82 (s, 1H), 8.15 (s, 1H), 7.75 (d, J=9.0 Hz, 1H), 7.69 (d, J=2.0 Hz, 1H), 7.49 (d, J=7.5 Hz, 1H), 7.38-7.31 (m, 5H), 7.26-7.24 (m, 1H), 6.04 (dd, J=7.5, 2.5 Hz, 1H), 5.69 (d, J=3.0 Hz, 1H), 5.51 (q, J=6.5 Hz, 1H), 4.77-4.75 (m, 2H), 3.66-3.63 (m, 2H), 3.46-3.45 (m, 2H), 3.00-2.99 (m, 2H), 1.93 (m, 2H), 1.78-1.75 (m, 2H), 1.51 (d, J=6.5 Hz, 3H); ESI MS m/z 429 [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe reaction mixture was filtered through a thin layer of Celite
  3. washwashed with CH2Cl2
  4. concentrationthe filtrate was concentrated
  5. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 90:10)

Sources & evidence

ORD record
ord-763be9183ac7469aa9d5faf7c9373d78
Source dataset
uspto-grants-2012_09
Patent number
US08268868B2

Reaction notes

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