Ammonium Chloride → 3-cyclopropyl-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-indazol-4-amine

HRID 79459Notes

Reaction equation

HRID 79459 reaction equation
[CH:1]1([C:4]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][C:11]=3[N+:13]([O-])=O)[N:6]([CH2:16][C:17]3[S:18][C:19]([CH3:22])=[N:20][N:21]=3)[N:5]=2)[CH2:3][CH2:2]1.CCO.O.[Cl-].[NH4+]>ClCCl.[Fe]>[CH:1]1([C:4]2[C:12]3[C:11]([NH2:13])=[CH:10][CH:9]=[CH:8][C:7]=3[N:6]([CH2:16][C:17]3[S:18][C:19]([CH3:22])=[N:20][N:21]=3)[N:5]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 19096565Water ethanolHCID 672590452-((3-cyclopropyl-4-nitro-1H-indazol-1-yl)methyl)-5-methyl-1,3,4-thiadiazole

Product 1

HCID 672599493-cyclopropyl-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-indazol-4-amineYield 48.3%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-((3-cyclopropyl-4-nitro-1H-indazol-1-yl)methyl)-5-methyl-1,3,4-thiadiazole (61.7 mg, 0.196 mmol) in 4:1 EtOH/H2O (2 mL) was added iron powder (0.219 g, 3.91 mmol) and ammonium chloride (10.5 mg, 0.196 mmol). The reaction mixture was heated to reflux for three hours. The reaction mixture was cooled to ambient temperature, diluted with excess dichloromethane, and the resulting suspension was dried over anhydrous sodium sulfate. The solids were removed by filtration, and the filtrate was concentrated under reduced pressure. The crude product was dissolved in dichloromethane, passed through a silica plug, eluting with 10% MeOH/DCM, and concentrated under reduced pressure to afford the product (27 mg) as a yellow solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for three hours
  3. dry with materialthe resulting suspension was dried over anhydrous sodium sulfate
  4. customThe solids were removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. dissolutionThe crude product was dissolved in dichloromethane
  7. washeluting with 10% MeOH/DCM
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8b269023fbe949298cc573a557b4a31c
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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