Hydrochloric Acid → HCID 178432643, compound

HRID 1371226Notes

Reaction equation

HRID 1371226 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[NH:5][C:4]2=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:11][C:3]=12.[NH:18]1[CH:22]=[N:21][CH:20]=[N:19]1.C([O-])([O-])=O.[Na+].[Na+].Cl>CCOC(C)=O>[ClH:1].[CH3:8][C:6]1[NH:5][C:4]2=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:11][C:3]2=[C:2]([C:22]2[N:21]=[CH:20][NH:19][N:18]=2)[N:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 92571H-1,2,4-TriazoleHCID 10340Sodium CarbonateHCID 178432852HCID 178432852, compound

Product 1

HCID 178432643HCID 178432643, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
195 °C

Procedure

To an oven-dried, 50-mL, round-bottomed flask was added 4-chloro-2-methyl-6-phenylpyrrolo[3,2-d]pyrimidine (Example 1(e)) (350 mg, 1.44 mmol) followed by 1,2,4-triazole (Aldrich Chemical Company) (200 mg, 2.88 mmol) and solid Na2CO3 (610 mg, 5.76 mmol). The flask was purged with N2 and heated to 190-200° C. for 4 h. The reaction was allowed to cool to room temperature and the residue was dissolved in MeOH (25 mL). The remaining salts were filter off and the organic layer evaporated under reduced pressure. The residue was purified by silica gel chromatography with 50% EtOAc/hexanes as eluant to give 180 mg (45% yield) of an off white solid. The free base (168 mg, 0.608 mmol) was dissolved in hot EtOAc (15 mL) and anhydrous ethereal HCl (0.61 mL, 1.0 M soln, 0.61 mmol) was added dropwise. A precipitate formed and the reaction was allowed to cool to room temperature and stirred for 1 h. The solid was filtered off and dried under vacuum at 60° C. overnight to give 182 mg (96% yield) of an off white solid. Mp: 264-265° C. 1H NMR (DMSO-d6; 400 MHz): d 2.77 (s, 3), 7.22 (s, 1), 7.57 (m, 3), 8.10 (d, 2, J=5.5), 8.6 (d, 1, J=3.4), 9.64 (d, 1, J=4.2), 11.87 (br m, 1). MS m/z: 277.0 (M+1); 275 (M−1).

Workup

  1. customThe flask was purged with N2
  2. temperatureto cool to room temperature
  3. dissolutionthe residue was dissolved in MeOH (25 mL)
  4. filtrationThe remaining salts were filter off
  5. customthe organic layer evaporated under reduced pressure
  6. customThe residue was purified by silica gel chromatography with 50% EtOAc/hexanes as eluant
  7. customto give 180 mg (45% yield) of an off white solid
  8. customA precipitate formed
  9. temperatureto cool to room temperature
  10. filtrationThe solid was filtered off
  11. customdried under vacuum at 60° C. overnight
  12. customto give 182 mg (96% yield) of an off white solid

Sources & evidence

ORD record
ord-fe38666c8b4b478ab5d07dcd951e60ac
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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