Hydrochloric Acid → 5-Chloro-4-(piperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 398233Notes

Reaction equation

HRID 398233 reaction equation
Cl[C:2]1[C:3]2[C:10]([Cl:11])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[NH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.O.Cl>C(O)(C)(C)C>[Cl:11][C:10]1[C:3]2[C:2]([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)=[N:7][CH:6]=[N:5][C:4]=2[NH:8][CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 8082PiperidineHCID 111060924,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 98161255-Chloro-4-(piperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidineYield 63.4%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

The product from Method R (57 mg, 0.3 mmol) was suspended in 3.0 mL of tert-butanol and to this solution was added piperidine (90 μL, 0.9 mmol) and the resulting system heated at reflux for 1 h. The reaction mixture was cooled to room temperature and water was added (4.0 mL). The solution was adjusted to pH 1 with 1 N HCl and then washed with ether. The aqueous layer was removed and adjusted to pH 12 with 2 N NaOH. The solution was then extracted 2×15 mL with dichloromethane and the combined organics washed with water then brine and dried over MgSO4. Evaporation of solvent afforded 45 mg of a yellow solid that was purified by silica-gel chromatography (3:1 ethyl acetate/hexanes) to yield 23 mg (32%) of the title compound as a light yellow solid. Mp 170-172° C. 1H NMR (400 MHz, CDCl3) δ: 1.67 -1.74 (m, 6H), 3.65-3.67 (m, 4H), 7.10 (s, 1H), 8.31 (s, 1H). LRMS: 237 (M+1).

Workup

  1. temperaturethe resulting system heated
  2. temperatureat reflux for 1 h
  3. washwashed with ether
  4. customThe aqueous layer was removed
  5. extractionThe solution was then extracted 2×15 mL with dichloromethane
  6. washthe combined organics washed with water
  7. dry with materialbrine and dried over MgSO4
  8. customEvaporation of solvent

Sources & evidence

ORD record
ord-8193996134c34b35aa687bb658e2d8ba
Source dataset
uspto-grants-2003_08
Patent number
US06610847B2

Reaction notes

Loading…