1H-Indazol-5-amine → Rho-Kinase-IN-3

HRID 734659Notes

Reaction equation

HRID 734659 reaction equation
[CH3:1][C:2]1[NH:3][C:4](=[O:21])[CH2:5][CH:6]([C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=2)[C:7]=1[C:8](O)=[O:9].[NH:22]1[C:30]2[C:25](=[CH:26][C:27]([NH2:31])=[CH:28][CH:29]=2)[CH:24]=[N:23]1>CN(C=O)C>[NH:22]1[C:30]2[C:25](=[CH:26][C:27]([NH:31][C:8]([C:7]3[CH:6]([C:11]4[CH:20]=[CH:19][C:18]5[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=5)[CH:12]=4)[CH2:5][C:4](=[O:21])[NH:3][C:2]=3[CH3:1])=[O:9])=[CH:28][CH:29]=2)[CH:24]=[N:23]1

Participants

4

Reactant 2

HCID 880121H-Indazol-5-amineHCID 160998652-Methyl-4-(2-naphthalenyl)-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylic acid

Product 1

HCID 11269477Rho-Kinase-IN-3Yield 22.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The product of step 2 (450 mg, 1.60 mmol, 1 equiv) was combined with 1H-indazol-5-amine (212 mg, 1.60 mmol, 1 equiv) and polystyrene-bound carbodiimide (1.78 g, 1.1 mmol/g, 1.97 mmol, 1.2 equiv) in 6 mL DMF. The reaction mixture was stirred for 22 hours at room temperature. The resin was removed by filtration and washed alternately with CH2Cl2 and MeOH, ending with CH2Cl2. The volatile solvents were removed en vacuo and water was added, providing a solid residue. The residue was triturated with ethyl acetate, affording 140 mg of the title compound as a white crystalline solid. MS (ES+) m/e 397 [M+H]+

Workup

  1. customThe resin was removed by filtration
  2. washwashed alternately with CH2Cl2 and MeOH
  3. customThe volatile solvents were removed en vacuo and water
  4. additionwas added
  5. customproviding a solid residue
  6. customThe residue was triturated with ethyl acetate

Sources & evidence

ORD record
ord-5716b9cbeb704cdc87f8e54ddf2adac0
Source dataset
uspto-grants-2009_09
Patent number
US07592357B2

Reaction notes

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