1H-Indazole → HCID 59148074, compound

HRID 1746112Notes

Reaction equation

HRID 1746112 reaction equation
N1C2C(=CC=CC=2)C=N1.[F:10][C:11]([F:22])([F:21])[C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][N:16]=[CH:15]2.C([O-])([O-])=O.[K+].[K+].[Cl:29][C:30]1[CH:37]=[CH:36][C:33]([CH2:34]Br)=[CH:32][CH:31]=1>CN(C=O)C.O>[Cl:29][C:30]1[CH:37]=[CH:36][C:33]([CH2:34][N:17]2[C:18]3[C:14](=[CH:13][C:12]([C:11]([F:10])([F:21])[F:22])=[CH:20][CH:19]=3)[CH:15]=[N:16]2)=[CH:32][CH:31]=1.[Cl:29][C:30]1[CH:37]=[CH:36][C:33]([CH2:34][N:16]2[CH:15]=[C:14]3[C:18]([CH:19]=[CH:20][C:12]([C:11]([F:10])([F:21])[F:22])=[CH:13]3)=[N:17]2)=[CH:32][CH:31]=1

Participants

8

Reactant 4

HCID 92211H-IndazoleHCID 11430Potassium CarbonateHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 214092225-(Trifluoromethyl)-1H-indazole

Product 2

HCID 59148074HCID 59148074, compoundYield 15%HCID 59148154HCID 59148154, compoundYield 7.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Indazole compounds can be synthesized according to methods disclosed in the literature, e.g. Lukin et al. J. Org. Chem. 2006, 71, 8166-8172 and Souers et al. J. Med. Chem. 2005, 48, 1318-1321. A mixture of 5-(trifluoromethyl)-1H-indazole 3a (0.46 g, 2.5 mmol), K2CO3 (1.04 g, 7.5 mmol) in DMF (8 mL) was stirred at room temperature for 30 min. To the mixture was added p-chlorobenzyl bromide (0.77 g, 3.75 mmol). The resulting mixture was heated at 60° C. for 6 h. After cooling, the mixture was poured into water (30 mL). The precipitate was filtered and washed with water and dried. The crude product was purified by chromatography (hexane/dichloromethane, 1:1 to 1:3) to give 1-(4-chlorobenzyl)-5-(trifluoromethyl)-1H-indazole 3b (120 mg, 15%) and 2-(4-chlorobenzyl)-5-(trifluoromethyl)-2H-indazole 3c (60 mg, 7.7%).

Workup

  1. temperatureThe resulting mixture was heated at 60° C. for 6 h
  2. temperatureAfter cooling
  3. filtrationThe precipitate was filtered
  4. washwashed with water
  5. customdried
  6. customThe crude product was purified by chromatography (hexane/dichloromethane, 1:1 to 1:3)

Sources & evidence

ORD record
ord-17cf9d8727524e33a370a40d6842b48a
Source dataset
uspto-grants-2015_10
Patent number
US09149463B2

Reaction notes

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