1H-indazol-3-amine → HCID 65855926, compound

HRID 522624Notes

Reaction equation

HRID 522624 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([NH2:10])=[N:2]1.[OH-].[K+].Cl.Cl[CH2:15][C:16]1[N:17]=[C:18]([CH3:21])[S:19][CH:20]=1.[H-].[Na+]>CS(C)=O.O>[CH3:21][C:18]1[S:19][CH:20]=[C:16]([CH2:15][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]([NH2:10])=[N:2]2)[N:17]=1

Participants

7

Reactant 4

HCID 133991H-indazol-3-amineHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 27342034-(Chloromethyl)-2-methyl-1,3-thiazole--hydrogen chloride (1/1)

Product 1

HCID 65855926HCID 65855926, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent3×HCID 962WaterSolvent

Procedure

A solution of 1H-indazol-3-amine (ABCR, 700 mg, 5.26 mmol) in anhydrous DMSO (10 ml) was added to a suspension of potassium hydroxide (PANREAC, 737 mg, 13.14 mmol) in anhydrous DMSO (40 mL) and this mixture was stirred for 10 min. A solution of 4-(chloromethyl)-2-methyl-1,3-thiazole hydrochloride (BUTTPARK, 776 mg, 5.26 mmol) and sodium hydride (ALDRICH, 126 mg, 5.26 mmol) in anhydrous DMSO (10 mL) was added dropwise to the mixture. Reaction was stirred at room temperature for 32 hours. Mixture of reaction was poured into water (100 mL) and extracted using DCM (4×100 mL). The combined organics were washed with water:brine (1:1) (100 mL) and dried over MgSO4 (anh), filtered and concentrated to dryness. Residue was purified using silica chromatography column using a linear gradient of DCM/MeOH (0%->5%) as eluents to give the title compound 1-[(2-methyl-1,3-thiazol-4-yl)methyl]-1H-indazol-3-amine (988 mg, 4.04 mmol, 77% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm: 7.67-7.69 (m, 1H), 7.40-7.43 (m, 1H), 7.23-7.28 (m, 1H), 7.07 (s, 1H), 6.90-6.90 (m, 1H), 5.46 (br s, 2H), 5.31 (s, 2H), 2.57 (s, 3H). [ES+MS] m/z 245 (MH+).

Workup

  1. customReaction
  2. stirringwas stirred at room temperature for 32 hours
  3. additionMixture of reaction
  4. extractionextracted
  5. washThe combined organics were washed with water:brine (1:1) (100 mL)
  6. dry with materialdried over MgSO4 (anh)
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customResidue was purified

Sources & evidence

ORD record
ord-4380128cb22c466cbff4b03517b11cc5
Source dataset
uspto-grants-2016_05
Patent number
US09334265B2

Reaction notes

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