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

HRID 988827Notes

Reaction equation

HRID 988827 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.C(O)(C)(C)C.[NH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.Cl>O>[Cl:11][C:10]1[C:3]2[C:2]([N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)=[N:7][CH:6]=[N:5][C:4]=2[NH:8][CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 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 962WaterSolvent

Procedure

The product from Method I (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 hour. 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 hour
  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-f23272e2fd1b4bb5aa90d279122662a9
Source dataset
uspto-grants-2003_10
Patent number
US06635762B1

Reaction notes

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