Dimethyl Sulfoxide → HCID 86676435, compound

HRID 1892889Notes

Reaction equation

HRID 1892889 reaction equation
[OH-].[K+].[CH3:3][O:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7]([NH2:14])=[N:8][NH:9]2.ClC[C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[C:20]#[N:21].O.[CH3:26]S(C)=O>C1CCCCC1.C(OCC)(=O)C>[NH2:14][C:7]1[C:6]2[C:10](=[CH:11][CH:12]=[CH:13][C:5]=2[O:4][CH3:3])[N:9]([CH2:26][C:18]2[CH:17]=[CH:24][CH:23]=[CH:22][C:19]=2[C:20]#[N:21])[N:8]=1

Participants

8

Reactant 5

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 14797Potassium HydroxideHCID 5221263-(Chloromethyl)benzonitrileHCID 185260534-Methoxy-1H-indazol-3-amine

Product 1

HCID 86676435HCID 86676435, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ground potassium hydroxide (6.75 g, 120 mmol) in DMSO (300 mL) at room temperature under nitrogen was added 4-(methyloxy)-1H-indazol-3-amine (for a preparation see Intermediate 1) (7.85 g, 48.1 mmol), and this gave a deep red solution. After 5 minutes 3-(chloromethyl)benzonitrile (8.84 g, 58.3 mmol) was added in one portion. The reaction mixture was stirred for 20 minutes and then poured into water (500 mL), forming an emulsion. This was extracted using chloroform (3×500 mL). The combined organic solutions were washed with water (400 mL) and passed through a hydrophobic frit. The solvent was removed in vacuo, the residue was applied to a 340 g silica cartridge, and eluted with a gradient of 0-100% ethyl acetate in cyclohexane over 8CV. This gave an orange solid which was treated with ethyl acetate (10 mL) and cyclohexane (90 mL). The solid was collected by filtration and washed with cyclohexane (50 mL). The solid was dried in vacuo to give the title compound (7.89 g, 59%) as a pale orange solid. LCMS (System A) RT=0.93 min, ES+ve m/z 279 (M+H)+.

Workup

  1. customthis gave a deep red solution
  2. customforming an emulsion
  3. extractionThis was extracted
  4. washThe combined organic solutions were washed with water (400 mL)
  5. customThe solvent was removed in vacuo
  6. washeluted with a gradient of 0-100% ethyl acetate in cyclohexane over 8CV
  7. customThis gave an orange solid which
  8. filtrationThe solid was collected by filtration
  9. washwashed with cyclohexane (50 mL)
  10. customThe solid was dried in vacuo

Sources & evidence

ORD record
ord-ce24b1ab08ae452d8f22b169acf31c7b
Source dataset
uspto-grants-2013_08
Patent number
US08507543B2

Reaction notes

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