Triethylamine → N-(1-benzyl-3-cyclopropyl-1H-indazol-4-yl)-7-(2-methoxyethoxy)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79265Notes

Reaction equation

HRID 79265 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]2[C:12]([C:15]([OH:17])=O)=[CH:13][N:14]=[C:8]2[CH:7]=1.C(Cl)(=O)C(Cl)=O.[CH2:24]([N:31]1[C:39]2[CH:38]=[CH:37][CH:36]=[C:35]([NH2:40])[C:34]=2[C:33]([CH:41]2[CH2:43][CH2:42]2)=[N:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C>ClCCl.CN(C)C=O>[CH2:24]([N:31]1[C:39]2[C:34](=[C:35]([NH:40][C:15]([C:12]3[N:9]4[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:7][C:8]4=[N:14][CH:13]=3)=[O:17])[CH:36]=[CH:37][CH:38]=2)[C:33]([CH:41]2[CH2:42][CH2:43]2)=[N:32]1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 667820257-(2-Methoxyethoxy)imidazo[1,2-a]pyridine-3-carboxylic acidHCID 672597331-benzyl-3-cyclopropyl-1H-indazol-4-amine

Product 1

HCID 67260162N-(1-benzyl-3-cyclopropyl-1H-indazol-4-yl)-7-(2-methoxyethoxy)imidazo[1,2-a]pyridine-3-carboxamideYield 29.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a magnetically stirred, ice cooled, suspension of 7-(2-methoxyethoxy)imidazo[1,2-a]pyridine-3-carboxylic acid (29.5 mg, 0.125 mmol) (prepared as in Example 1, steps A-D) in dichloromethane (1 mL) was added N,N-dimethylformamide (5 μL) followed by oxalyl chloride (79.7 μL, 0.159 mmol; 2M solution in dichloromethane). The mixture was stirred in a sealed vial and allowed to warm to ambient temperature. The vial was occasionally vented to allow gases to evolve. After 30 minutes a solution of 1-benzyl-3-cyclopropyl-1H-indazol-4-amine (35.0 mg, 0.133 mmol) in dichloromethane was added followed by triethylamine (27.8 μL; 0.199 mmol). The mixture was stirred for 24 hours and then concentrated under reduced pressure. The material was purified by preparative thin layer chromatography, eluting with 10% methanol in dichloromethane. Further purification was carried out eluting with hexane/ethyl acetate (3:1). The desired band was isolated and concentrated to give N-(1-benzyl-3-cyclopropyl-1H-indazol-4-yl)-7-(2-methoxyethoxy)imidazo[1,2-a]pyridine-3-carboxamide (17.5 mg). MS (APCI), positive scan, m/z=482.3 (M+H).

Workup

  1. temperatureice cooled
  2. stirringThe mixture was stirred in a sealed vial and
  3. stirringThe mixture was stirred for 24 hours
  4. concentrationconcentrated under reduced pressure
  5. customThe material was purified by preparative thin layer chromatography
  6. washeluting with 10% methanol in dichloromethane
  7. customFurther purification
  8. washwas carried out eluting with hexane/ethyl acetate (3:1)
  9. customThe desired band was isolated
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-25b74db5cb50436885222e073d343257
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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