1-Bromo-3-chloropropane → 6-(3-Chloropropoxy)-5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole

HRID 2112181

Reaction equation

[F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[OH:14])[N:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[N:9]=[CH:8]2.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:31][CH2:32][CH2:33][Cl:34]>CN(C=O)C.O.CCOCC>[Cl:34][CH2:33][CH2:32][CH2:31][O:14][C:13]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][N:10]2[CH2:15][CH:16]([CH3:18])[CH3:17])=[CH:6][C:5]=1[O:4][C:3]1[CH:19]=[CH:20][C:21]([F:23])=[CH:22][C:2]=1[F:1]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol (0.015 g, 0.05 mmol) in DMF (1 mL) was added Cs2CO3. The reaction mixture was stirred for 30 minutes before the addition of 1-bromo-3-chloropropane (0.01 g, 0.08 mmol) and then was heated to 80° C. for 25 hours. After cooling the mixture to room temperature, the reaction mixture was diluted with water and ether and the layers separated. The aqueous layer was extracted with ether and the combined organic layers were washed with 1N NaOH, water, and brine. The crude mixture was dried over Na2SO4 and concentrated under reduced pressure to afford the product with a small impurity. The crude mixture was used in the next reaction without further purification.

Workup

temperatureAfter cooling the mixture to room temperature
customthe layers separated
extractionThe aqueous layer was extracted with ether
washthe combined organic layers were washed with 1N NaOH, water, and brine
dry with materialThe crude mixture was dried over Na2SO4
concentrationconcentrated under reduced pressure
customto afford the product with a small impurity

Sources & evidence

ORD record: ord-5655c8e6440a469daed5742b79e7beb4
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07521447B2

Linked notes

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