Ammonium Chloride → 3-iodo-1-((2-methylthiazol-5-yl)methyl)-1H-indazol-4-amine

HRID 79452Notes

Reaction equation

HRID 79452 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-])=O)[N:4]([CH2:14][C:15]2N=C(C)S[CH:19]=2)[N:3]=1.[CH3:21][C:22]1[S:23]C(C(OCC)=O)=C[N:26]=1.[NH4+].[Cl-]>CCO.O.[Fe]>[I:1][C:2]1[C:10]2[C:9]([NH2:11])=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]([CH2:14][C:15]2[S:23][C:22]([CH3:21])=[N:26][CH:19]=2)[N:3]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 12808791Ethyl 2-methyl-1,3-thiazole-5-carboxylateHCID 672615074-((3-iodo-4-nitro-1H-indazol-1-yl)methyl)-2-methylthiazole

Product 1

HCID 672609553-iodo-1-((2-methylthiazol-5-yl)methyl)-1H-indazol-4-amine

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 19096565Water ethanolSolvent

Conditions

Temperature
85 °C

Procedure

To a solution 4-((3-iodo-4-nitro-1H-indazol-1-yl)methyl)-2-methylthiazole (prepared according the method of Example 15, Steps A-D, using ethyl 2-methylthiazole-5-carboxylate) in EtOH/H2O (8 mL/2 mL) was added iron (463 mg, 8.30 mmol) and NH4Cl (44.4 mg, 0.830 mmol). The reaction mixture was heated at 85° C. for 3 hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure. EtOAc/Et3N (40 mL/10 mL) was added to the residue. The mixture was heated at 85° C. for 20 minutes, cooled to 45° C., and filtered through Celite. The Celite pad was washed with MeOH (30 mL). The combined filtrate was concentrated under reduced pressure to remove EtOAc and MeOH. The aqueous suspension was extracted with DCM. The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to give the product (156 mg).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated under reduced pressure
  3. additionEtOAc/Et3N (40 mL/10 mL) was added to the residue
  4. temperatureThe mixture was heated at 85° C. for 20 minutes
  5. temperaturecooled to 45° C.
  6. filtrationfiltered through Celite
  7. washThe Celite pad was washed with MeOH (30 mL)
  8. concentrationThe combined filtrate was concentrated under reduced pressure
  9. customto remove EtOAc and MeOH
  10. extractionThe aqueous suspension was extracted with DCM
  11. dry with materialThe combined organic extracts were dried (Na2SO4)
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b7db519a758049d18cfb3b47d6db67d7
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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