Water → HCID 58054476, compound

HRID 1808579Notes

Reaction equation

HRID 1808579 reaction equation
[OH-].[K+].[F:3][C:4]1[CH:5]=[CH:6][C:7]([O:14][CH3:15])=[C:8]2[C:12]=1[NH:11][N:10]=[C:9]2[NH2:13].Cl[CH2:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=1)[C:21]#[N:22].O>CS(C)=O.ClCCl>[NH2:13][C:9]1[C:8]2[C:12](=[C:4]([F:3])[CH:5]=[CH:6][C:7]=2[O:14][CH3:15])[N:11]([CH2:17][C:18]2[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=2)[C:21]#[N:22])[N:10]=1

Participants

7

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 5221263-(Chloromethyl)benzonitrileHCID 580544601240518-37-9

Product 1

HCID 58054476HCID 58054476, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a fine suspension of ground potassium hydroxide (566 mg, 10.09 mmol) in dimethyl sulfoxide (5 mL) at room temperature under nitrogen was added a solution of 7-fluoro-4-(methyloxy)-1H-indazol-3-amine (for a preparation see Intermediate 43) (727 mg, 4.01 mmol) in dimethyl sulfoxide (2 mL). After 5 min the resulting dark brown solution was treated with 3-(chloromethyl)benzonitrile (730 mg, 4.82 mmol). The reaction mixture was stirred for 30 min and then the mixture was poured into water, forming an emulsion. This was extracted with DCM and the combined extracts were washed with water and passed through a hydrophobic frit. The aqueous was extracted with ethyl acetate and the combined organic solutions were washed with water and brine, dried (Na2SO4) and then combined with the initial DCM extracts and concentated in vacuo to leave a brown oil. The residue was loaded in dichloromethane to a silica 100 g cartridge and purified by chromatography on Flashmaster eluting with 0-100% ethyl acetate-cyclohexane over 40 min. The appropriate fractions were combined and evaporated in vacuo to give the required product (665 mg, 56%) as a yellow powder. LCMS (System A) RT=1.02 min, ES+ve m/z 297 (M+H)+.

Workup

  1. customforming an emulsion
  2. extractionThis was extracted with DCM
  3. washthe combined extracts were washed with water
  4. extractionThe aqueous was extracted with ethyl acetate
  5. washthe combined organic solutions were washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. customto leave a brown oil
  8. custompurified by chromatography on Flashmaster
  9. washeluting with 0-100% ethyl acetate-cyclohexane over 40 min
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-cf198e5bf38844989397526b422e0f79
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

Loading…