Water → 3-[(3-Amino-4-fluoro-1H-indazol-1-yl)methyl]benzonitrile

HRID 1874680Notes

Reaction equation

HRID 1874680 reaction equation
[OH-].[K+].[F:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6]([NH2:13])=[N:7][NH:8]2.[C:14]([C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH2:19]Br)#[N:15].O>CS(C)=O>[NH2:13][C:6]1[C:5]2[C:9](=[CH:10][CH:11]=[CH:12][C:4]=2[F:3])[N:8]([CH2:19][C:18]2[CH:17]=[C:16]([CH:23]=[CH:22][CH:21]=2)[C:14]#[N:15])[N:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 97249Benzonitrile, 3-(bromomethyl)-HCID 8179114-fluoro-1H-indazol-3-amine

Product 1

HCID 580543733-[(3-Amino-4-fluoro-1H-indazol-1-yl)methyl]benzonitrile

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a suspension of ground potassium hydroxide (0.483 g, 8.60 mmol) in anhydrous dimethyl sulfoxide (15 mL) at room temperature under nitrogen was added a solution of 4-fluoro-1H-indazol-3-amine (for a preparation see Intermediate 36) (0.52 g, 3.44 mmol) in anhydrous dimethyl sulfoxide (10 mL). The resulting deep red solution was treated after 10 minutes with 3-cyanobenzyl bromide (0.843 g, 4.30 mmol) in one portion. The reaction mixture was stirred for 30 min and then poured into water (100 mL), forming a yellow emulsion. This was extracted using chloroform (2×100 mL). The combined organic solutions were washed with water-brine (1:1) (100 mL), passed through a hydrophobic frit and evaporated in-vacuo to yield a red oil (2.263 g). The residue was applied to a 100 g silica SPE cartridge and purified by chromatography on Flashmaster II eluting with a 0-100% ethyl acetate in cyclohexane gradient over 80 min. Fractions 159-173 were combined and the solvent was evaporated in-vacuo to yield a yellow solid the title compound (0.77 g, 84%) LCMS (System B) RT=2.32 min, ES+ve m/z 267 (M+H)+.

Workup

  1. customforming a yellow emulsion
  2. extractionThis was extracted
  3. washThe combined organic solutions were washed with water-brine (1:1) (100 mL)
  4. customevaporated in-vacuo

Sources & evidence

ORD record
ord-b1e1016b61c542d1ba166c8d600168e8
Source dataset
uspto-grants-2012_11
Patent number
US08304446B2

Reaction notes

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