Hydrochloric Acid → N-(1-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride

HRID 79414Notes

Reaction equation

HRID 79414 reaction equation
[NH:1]1[CH:5]=[C:4]([CH2:6][N:7]2[C:15]3[C:10](=[C:11]([NH:16][C:17]([C:19]4[N:23]5[CH:24]=[CH:25][CH:26]=[CH:27][C:22]5=[N:21][CH:20]=4)=[O:18])[CH:12]=[CH:13][CH:14]=3)[C:9]([CH2:28][CH3:29])=[N:8]2)[CH:3]=[N:2]1.Br[CH2:31][CH:32]1[CH2:34][CH2:33]1.O.[OH-].[Cs+].[ClH:38]>CN(C=O)C>[ClH:38].[ClH:38].[CH:32]1([CH2:31][N:1]2[CH:5]=[C:4]([CH2:6][N:7]3[C:15]4[C:10](=[C:11]([NH:16][C:17]([C:19]5[N:23]6[CH:24]=[CH:25][CH:26]=[CH:27][C:22]6=[N:21][CH:20]=5)=[O:18])[CH:12]=[CH:13][CH:14]=4)[C:9]([CH2:28][CH3:29])=[N:8]3)[CH:3]=[N:2]2)[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 81503BromomethylcyclopropaneHCID 23679066Caesium hydroxide--water (1/1/1)HCID 67259648N-(1-((1H-pyrazol-4-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 67259456N-(1-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochlorideYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(1-((1H-pyrazol-4-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (20 mg, 0.052 mmol; prepared according to Example 21, Step A) in dry DMF (0.5 mL) was added (bromomethyl)cyclopropane (7.0 mg, 0.052 mmol) and cesium hydroxide hydrate (8.7 mg, 0.052 mmol). The mixture was stirred at ambient temperature for 60 minutes. The mixture was filtered, washed with methanol and ethyl acetate, and concentrated under reduced pressure. The residue was purified using preparative thin layer chromatography on silica, eluting with 10% methanol in dichloromethane. The product was dissolved in a mixture of dichloromethane and methanol. Hydrogen chloride (0.52 mmol; 2M solution in diethyl ether) was added and the solvent was removed under reduced pressure, followed by high vacuum to give N-(1-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride (5.6 mg). MS (APCI), positive scan, m/z=440.2 (M+H).

Workup

  1. filtrationThe mixture was filtered
  2. washwashed with methanol and ethyl acetate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified
  5. washeluting with 10% methanol in dichloromethane
  6. dissolutionThe product was dissolved in a mixture of dichloromethane and methanol
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-aae273661b554db1865e00aea73b65eb
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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