Piperidine → HCID 18511143, compound

HRID 635682Notes

Reaction equation

HRID 635682 reaction equation
NC1[NH:7][C:6]2=[CH:8][C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:10][C:5]2=C(O)N=1.P(Cl)(Cl)(Cl)=O.[C:23]([O-:26])([O-])=[O:24].[Na+].[Na+].N1CCC[CH2:31][CH2:30]1.O1CCOC[CH2:36]1>>[NH2:7][C:6]1[C:8]([CH3:36])=[C:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:10][C:5]=1[C:23]([O:26][CH2:30][CH3:31])=[O:24]

Participants

6

Reactant 5

HCID 8082PiperidineHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 312751,4-DioxaneHCID 178508918HCID 178508918, compound

Product 1

HCID 18511143HCID 18511143, compoundYield 27%

Conditions

Temperature
124 °C

Procedure

In a round-bottomed flask was added 2-amino-6-phenylpyrrolo[3,2-d]pyrimidin-4-ol (Example 66(d)) (0.26 g, 1.2 mmol) and phosphorus oxychloride (2.7 mL, 28.8 mmol). The mixture was heated in a 124° C. oil bath for 24 h, then excess POCl3 was removed in vacuo to afford a brown residue. Ice-cold water was added and the pH of the solution was adjusted to pH 8 (pH paper) by adding aqueous Na2CO3. The resulting precipitate was collected by filtration, washed with water and then dried in a vacuum oven at 40° C. to give a brown solid. This material was transferred to a round-bottomed flask and heated with piperidine (0.57 mL, 5.75 mmol) and dioxane (8 mL) in a 110° C. oil bath for 15 h. Most of the solvent was then evaporated in vacuo. Chloroform was added to the residue, and the orgainc layer was separated, washed with water, dried over Na2SO4 and concentrated in vacuo to give a brown foam. Purification by flash chromatography on silica gel with 100:2:1 CHCl3:MeOH:Et3N as eluent afforded 92 mg (27%) of the title compound as a tan solid. The above material (78 mg, 0.27 mmol) was dissolved in a minimal amount of CHCl3 and HCl (0.6 mL of a 1M soln in ether, 0.6 mmol) was added dropwise. The mixture was stirred at room temperature for 20 min, and the solvent was evaporated in vacuo to give a tan foam. Recrystallization from MeOH/H2O gave 26 mg (6%) of the title compound as off-white crystals. Mp: >300° C. (dec). 1H NMR (DMSO-d6; 500 MHz): δ 1.66-1.67 (m, 6), 3.97 (m, 4), 6.66 (s, 1), 7.32 (br s, 2), 7.45-7.53 (m, 3), 7.87 (d, 2, J=7.26), 11.53 (br s, 1), 12.51 (br s, 1); MS m/z: 294 (M+1), 292 (M−1). Anal. Calcd for C17H19N5.HCl.0.2H2O: C, 61.28%; H, 6.16%; N, 21.02%; Cl, 10.64%. Found: C, 61.28%; H, 6.15%; N, 21.06%; Cl, 10.78%.

Workup

  1. customexcess POCl3 was removed in vacuo
  2. customto afford a brown residue
  3. additionIce-cold water was added
  4. filtrationThe resulting precipitate was collected by filtration
  5. washwashed with water
  6. customdried in a vacuum oven at 40° C.
  7. customto give a brown solid
  8. customThis material was transferred to a round-bottomed flask
  9. customMost of the solvent was then evaporated in vacuo
  10. additionChloroform was added to the residue
  11. customthe orgainc layer was separated
  12. washwashed with water
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated in vacuo
  15. customto give a brown foam
  16. customPurification by flash chromatography on silica gel with 100:2:1 CHCl3

Sources & evidence

ORD record
ord-3c2649986113434a942df73b62ffa85f
Source dataset
uspto-grants-2001_02
Patent number
US06187777B1

Reaction notes

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