Dimethylformamide → N-(3-ethyl-1-((1-ethyl-1H-pyrazol-5-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79343Notes

Reaction equation

HRID 79343 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([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)=[N:2]1.CN(C=O)C.Br[CH2:36][CH3:37].O.[OH-].[Cs+]>>[CH2:28]([C:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][C:11]=2[NH:16][C:17]([C:19]2[N:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]3=[N:21][CH:20]=2)=[O:18])[N:7]([CH2:6][C:3]2[N:2]([CH2:36][CH3:37])[N:1]=[CH:5][CH:4]=2)[N:8]=1)[CH3:29]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6332Ethyl BromideHCID 23679066Caesium hydroxide--water (1/1/1)HCID 178437952HCID 178437952, compound

Product 1

HCID 67260647N-(3-ethyl-1-((1-ethyl-1H-pyrazol-5-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 4.8%

Procedure

To N-(1-((1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (40 mg, 0.10 mmol) in dry DMF (519 μl, 0.10 mmol) was added bromoethane (11 mg, 0.10 mmol), cesium hydroxide hydrate (17 mg, 0.10 mmol) and 4 angstrom molecular sieves. The reaction mixture was stirred for one hour, filtered through an Acrodisk, rinsed with DCM and MeOH, and concentrated under a nitrogen stream to a residue. Preparative thin layer chromatography eluting with 10% MeOH, 0.5% NH4OH in CHCl3 provided the desired product (2 mg). MS (ES+APCI) m/z=414 (M+H). (The other regioisomer, N-(1-((1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide, was also isolated and was utilized in Example 40).

Workup

  1. filtrationfiltered through an Acrodisk
  2. washrinsed with DCM and MeOH
  3. concentrationconcentrated under a nitrogen stream to a residue
  4. washPreparative thin layer chromatography eluting with 10% MeOH, 0.5% NH4OH in CHCl3

Sources & evidence

ORD record
ord-b7672f77a1f3445cbf3aea985213a9fa
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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