Stannous Chloride → 5-[(3,5-difluorobenzyl)oxy]-1H-indazol-3-amine

HRID 1803842Notes

Reaction equation

HRID 1803842 reaction equation
[N:1]([O-])=O.[Na+].[NH2:5][C:6]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=2)=[CH:10][C:7]=1[C:8]#[N:9].[Sn](Cl)Cl>O.Cl.[OH-].[Na+]>[F:23][C:18]1[CH:17]=[C:16]([CH:21]=[C:20]([F:22])[CH:19]=1)[CH2:15][O:14][C:11]1[CH:10]=[C:7]2[C:6](=[CH:13][CH:12]=1)[NH:5][N:9]=[C:8]2[NH2:1]

Participants

7

Reactant 3

HCID 24479Stannous ChlorideHCID 23668193Sodium NitriteHCID 669971222-Amino-5-[(3,5-difluorobenzyl)oxy]benzonitrile

Product 1

HCID 669970485-[(3,5-difluorobenzyl)oxy]-1H-indazol-3-amineYield 76.4%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

A solution of sodium nitrite (13 gr, 190 mmol) in water (15 mL) was added dropwise to a cooled (0° C.) mixture of 2-amino-5-[(3,5-difluorobenzyl)oxy]benzonitrile (42.9 g, 165 mmol) in 37% hydrochloric acid (340 mL). After 2 hours, the resulting reaction mixture was added over a period of 1 hour to a previously prepared cooled suspension of tin(II) chloride (250 gr, 1.32 mol) in 37% hydrochloric acid (286 mL) trying to keep the temperature below 10° C. After 1 hour, the resulting reaction mixture was diluted with water (400 mL) and 35% NaOH (735 mL) was added to obtain a pH value of 9-10. The reaction mixture was extracted with EtOAc (1 L) and washed with EtOAc (2×0.5 L). Collected organic phases were dried over sodium sulfate, filtered and evaporated to dryness. The crude residue was purified by chromatography on silica gel using dichloromethane/7M NH3 in MeOH 96:4 as the eluant, affording 34.7 g of the title compound (76% yield).

Workup

  1. temperaturea cooled
  2. customthe resulting reaction mixture
  3. additionwas added over a period of 1 hour to
  4. customa previously prepared
  5. temperaturecooled
  6. customthe temperature below 10° C
  7. waitAfter 1 hour
  8. customthe resulting reaction mixture
  9. additionwas added
  10. customto obtain a pH value of 9-10
  11. extractionThe reaction mixture was extracted with EtOAc (1 L)
  12. washwashed with EtOAc (2×0.5 L)
  13. dry with materialCollected organic phases were dried over sodium sulfate
  14. filtrationfiltered
  15. customevaporated to dryness
  16. customThe crude residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-a71d9413702a42adb66a001cc267e346
Source dataset
uspto-grants-2013_01
Patent number
US08354399B2

Reaction notes

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