Hydrochloric Acid → N-(4-methoxyphenyl)-N,5-dimethylfuro[2,3-d]pyrimidin-4-amine

HRID 1842590Notes

Reaction equation

HRID 1842590 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[C:11]3[C:18]([CH3:19])=[CH:17][O:16][C:12]=3[N:13]=[CH:14][N:15]=2)=[CH:5][CH:4]=1.[H-].[Na+].S(OC)(O[CH3:26])(=O)=O.Cl>CO.C(Cl)(Cl)Cl.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]([CH3:26])[C:10]2[C:11]3[C:18]([CH3:19])=[CH:17][O:16][C:12]=3[N:13]=[CH:14][N:15]=2)=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 57428969N-(4-methoxyphenyl)-5-methylfuro[2,3-d]pyrimidin-4-amine

Product 1

HCID 44555430N-(4-methoxyphenyl)-N,5-dimethylfuro[2,3-d]pyrimidin-4-amine

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a 25 mL round bottom flask was weighed 7 (51 mg, 0.2 mmol) and was added DMF (2 mL) to afford a solution. The flask was purged with argon for five min followed by cooling down to 0° C. using ice bath. Sodium hydride (14.4 mg, 0.6 mmol) was added to the solution at 0° C. The solution was stirred for 30 min at 0° C. under argon atmosphere. Dimethyl sulfate (75.7 mg; ≈57 μl; 0.6 mmol) was injected to the reaction mixture and the flask was warmed to room temperature. The mixture was stirred at room temperature for another 3 h at the end of which 1 N Hydrochloric acid (5 mL) was added carefully to quench the reaction followed by water (20 mL) to afford a precipitate. Product was extracted using ethyl acetate (10 mL×2). Combined organic extracts were washed with brine (10 mL) dried (anhydrous sodium sulfate) and concentrated under reduced pressure. Silica gel (200 mg) was added and solvent evaporated to afford a plug. Column chromatography by elution with hexanes:ethyl acetate (5:1) afforded AAG16 (20 mg; 37%) as light brown semisolid; which was triturated withl hexanes to afford light brown solid. TLC Rf0.79 (CHCl3:MeOH, 10:1); mp 84-85.6° C.; 1HNMR (400 MHz) (DMSO-d6): δ 1.036-1.039 (d, 3H, CH3, J=1.2 Hz); 3.423 (s, 3H, NCH3), 3.752 (s, 3H, OCH3), 6.944-6.967 (d, 2H, C6H4, J=9.2 Hz), 7.176-7.199 (d, 2H, C6H4, J=9.2 Hz), 7.505-7.508 (d, 1H, C6-CH, J=1.2 Hz), 8.234 (s, 1H, C2-CH). Anal. Calcd for C15H15N3O2.0.28 C6H14.0.05 HCl: C, 67.84; H, 6.48; N, 14.22; Found: C, 67.89; H, 6.18; N, 14.06.

Workup

  1. customTo a 25 mL round bottom flask was weighed
  2. customto afford a solution
  3. customThe flask was purged with argon for five min
  4. temperaturethe flask was warmed to room temperature
  5. additionwas added carefully
  6. customto quench the reaction
  7. customto afford a precipitate
  8. extractionProduct was extracted
  9. washCombined organic extracts were washed with brine (10 mL)
  10. dry with materialdried (anhydrous sodium sulfate)
  11. concentrationconcentrated under reduced pressure
  12. additionSilica gel (200 mg) was added
  13. customsolvent evaporated
  14. customto afford a plug
  15. washColumn chromatography by elution with hexanes:ethyl acetate (5:1)
  16. customafforded AAG16 (20 mg; 37%) as light brown semisolid
  17. customwhich was triturated withl hexanes
  18. customto afford light brown solid

Sources & evidence

ORD record
ord-692f4f840692475bbeda995ccb973d14
Source dataset
uspto-grants-2015_02
Patent number
US08946239B2

Reaction notes

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