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

HRID 1808577Notes

Reaction equation

HRID 1808577 reaction equation
[OH-].[K+].[Cl: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[Cl: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 3134443-Amino-4-chloroindazole

Product 1

HCID 580544833-[(3-Amino-4-chloro-1H-indazol-1-yl)methyl]benzonitrile

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a suspension of ground potassium hydroxide (421 mg, 7.50 mmol) in anhydrous dimethyl sulfoxide (5 mL) at room temperature under nitrogen was added a solution of 4-chloro-1H-indazol-3-amine (for a preparation see Intermediate 40) (503 mg, 3.0 mmol) in anhydrous dimethyl sulfoxide (15 mL). After 30 minutes 3-cyanobenzyl bromide (Aldrich) (735 mg, 3.75 mmol) was added in one portion. The reaction mixture was stirred for 2 hours. The reaction mixture was poured into water (200 mL), forming a yellow/brown emulsion. This was extracted using chloroform (2×200 mL). The combined organic solutions were washed with water:brine (1:1) (200 mL), passed through a hydrophobic frit, and evaporated in-vacuo to yield a brown oil. The oil was applied to a 100 g silica SPE cartridge and purified by chromatography on Flashmaster II using a 0-100% ethyl acetate in cyclohexane gradient over 80 min. Fractions 32-34 were combined and the solvent was evaporated in-vacuo to yield the title compound as an off white solid (216 mg, 25%). LCMS (System B) RT=2.51 min, ES+ve m/z 283 (M+H)+.

Workup

  1. customforming a yellow/brown emulsion
  2. extractionThis was extracted
  3. washThe combined organic solutions were washed with water:brine (1:1) (200 mL)
  4. customevaporated in-vacuo
  5. customto yield a brown oil
  6. custompurified by chromatography on Flashmaster II
  7. customover 80 min
  8. customthe solvent was evaporated in-vacuo

Sources & evidence

ORD record
ord-45e9d70ba7894857bae991a395e0830c
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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