Ammonium Hydroxide → N-(4-chloro-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2,2-dimethylpropanamide

HRID 1842587Notes

Reaction equation

HRID 1842587 reaction equation
[CH3:1][C:2]([CH3:18])([CH3:17])[C:3]([NH:5][C:6]1[NH:7][C:8](=O)[C:9]2[NH:14][C:13]([CH3:15])=[CH:12][C:10]=2[N:11]=1)=[O:4].[OH-].[NH4+].P(Cl)(Cl)([Cl:23])=O>>[Cl:23][C:8]1[C:9]2[NH:14][C:13]([CH3:15])=[CH:12][C:10]=2[N:11]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:18])([CH3:17])[CH3:1])[N:7]=1

Participants

4

Reactant 3

HCID 14923Ammonium HydroxideHCID 24813Phosphorus oxychlorideHCID 1357974532,2-Dimethyl-N-(6-methyl-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yl)propanamide

Product 1

HCID 24754903N-(4-chloro-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-2-yl)-2,2-dimethylpropanamideYield 86%

Procedure

To a 100-mL round-bottomed flask was added 9 (1.16 g, 4.67 mmol) suspended in 30 mL phosphorus oxychloride. The reaction mixture was heated at reflux with stirring in an anhydrous atmosphere for 3 h. The dark orange solution was allowed to cool to room temperature and concentrated in vacuo. Water (20 mL) was then added to the residue at 0° C. with vigorous stirring to give an exothermic reaction. Concentrated aqueous ammonium hydroxide was added to pH 5 to give a precipitate, which was collected by filtration, washed with water (3×5 mL), and dried in vacuo. The crude product was purified by silica gel column chromatography with 2% MeOH/CHCl3. Recrystallization from MeOH afforded 1.07 g (86%) of 10 as a white solid: TLC Rf0.35 (MeOH/CHCl3, 1:10); mp 162-163° C.; 1H NMR (DMSO-d6) δ 1.19 (s, 9 H), 2.47 (s, 3 H), 6.33 (s, 1 H), 9.85 (s, 1 H), 12.07 (s, 1 H) Anal. (C12H15ClN4O) C, H, N, Cl.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux
  3. concentrationconcentrated in vacuo
  4. additionWater (20 mL) was then added to the residue at 0° C.
  5. stirringwith vigorous stirring
  6. customto give
  7. customan exothermic reaction
  8. customto give a precipitate, which
  9. filtrationwas collected by filtration
  10. washwashed with water (3×5 mL)
  11. customdried in vacuo
  12. customThe crude product was purified by silica gel column chromatography with 2% MeOH/CHCl3
  13. customRecrystallization from MeOH

Sources & evidence

ORD record
ord-afd2abdded334a1295e09490b692dc78
Source dataset
uspto-grants-2015_02
Patent number
US08946239B2

Reaction notes

Loading…