Hydrochloric Acid → Edicotinib Hydrochloride

HRID 456014Notes

Reaction equation

HRID 456014 reaction equation
[CH3:1][C:2]1([CH3:34])[CH2:7][CH2:6][C:5]([C:8]2[C:13]([NH:14][C:15]([C:17]3[NH:18][CH:19]=[C:20]([C:22]#[N:23])[N:21]=3)=[O:16])=[CH:12][CH:11]=[C:10]([CH:24]3[CH2:29][C:28]([CH3:31])([CH3:30])[O:27][C:26]([CH3:33])([CH3:32])[CH2:25]3)[N:9]=2)=[CH:4][CH2:3]1.[ClH:35]>CCO>[ClH:35].[CH3:1][C:2]1([CH3:34])[CH2:7][CH2:6][C:5]([C:8]2[C:13]([NH:14][C:15]([C:17]3[NH:18][CH:19]=[C:20]([C:22]#[N:23])[N:21]=3)=[O:16])=[CH:12][CH:11]=[C:10]([CH:24]3[CH2:25][C:26]([CH3:33])([CH3:32])[O:27][C:28]([CH3:31])([CH3:30])[CH2:29]3)[N:9]=2)=[CH:4][CH2:3]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 178424627HCID 178424627, compound

Product 1

HCID 178424628Edicotinib HydrochlorideYield 38%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 4-cyano-1H-imidazole-2-carboxylic acid[2-(4,4-dimethyl-cyclohex-1-enyl)-6-(2,2,6,6-tetramethyl-tetrahydro-pyran-4-yl)-pyridin-3-yl]-amide (49.2 mg, 0.107 mmol, as prepared in Example 15, step (h)) in EtOH (2 mL) was treated with HCl (26.6 μL, 0. 107 mmol, 4 M in dioxane) at room temperature for 1.5 h. The solvents were evaporated in vacuo, and the residue was dried under high vacuum overnight. The solid was dissolved in a minimum amount of EtOH (900 μL) with sonication and heating. While warm, the solution was slowly treated with hexanes (3 mL) to the cloud point. The mixture was heated again until clear, the sides of the vial were scratched, and the mixture was allowed to cool. The solid was filtered and air-dried to afford the title compound (20mg, 38%) as white crystals. 1H-NMR (CD3OD; 400 MHz): δ 9.17 (d, 1H, J=8.4 Hz), 8.10 (s, 1H), 7.95 (d, 1H, J=8.4 Hz), 6.38-6.32 (m, 1H), 3.76-3.65 (m, 1H), 2.54-2.46 (m, 2H), 2.25-2.19 (m, 2H), 1.98-1.91 (m, 2H), 1.76-1.65 (m, 4H), 1.43 (s, 6H), 1.30 (s, 6H), 1.15 (s, 6H). Mass spectrum (APCI, m/z): Calcd. for C27H35N5O2, 462.3 (M+H), found 462.3.

Workup

  1. customThe solvents were evaporated in vacuo
  2. customthe residue was dried under high vacuum overnight
  3. dissolutionThe solid was dissolved in a minimum amount of EtOH (900 μL) with sonication
  4. temperatureheating
  5. temperatureWhile warm
  6. additionthe solution was slowly treated with hexanes (3 mL) to the cloud point
  7. temperatureThe mixture was heated again until clear, the sides of the
  8. temperatureto cool
  9. filtrationThe solid was filtered
  10. customair-dried

Sources & evidence

ORD record
ord-105d72d6190542a1927fb2785e62ef36
Source dataset
uspto-grants-2013_07
Patent number
US08497376B2

Reaction notes

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