Hydrochloric Acid → ((R)-1-Phenyl-ethyl)-[6-(4-piperazin-1-ylmethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine

HRID 2252794Notes

Reaction equation

HRID 2252794 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[NH:38][C:24]4[N:25]=[CH:26][N:27]=[C:28]([NH:29][C@@H:30]([C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)[CH3:31])[C:23]=4[CH:22]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>O1CCOCC1.CO>[C:32]1([C@H:30]([NH:29][C:28]2[C:23]3[CH:22]=[C:21]([C:18]4[CH:19]=[CH:20][C:15]([CH2:14][N:11]5[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]5)=[CH:16][CH:17]=4)[NH:38][C:24]=3[N:25]=[CH:26][N:27]=2)[CH3:31])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 59645279HCID 59645279, compound

Product 1

HCID 11350462((R)-1-Phenyl-ethyl)-[6-(4-piperazin-1-ylmethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
55 °C

Procedure

4-{4-[4-((R)-1-Phenyl-ethylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzyl}-piperazine-1-carboxylic acid tert-butyl ester (1.8 g, 3.5 mmol) is dissolved in 150 mL of dioxane by gentle warming. To this solution is added a solution of 4 N hydrochloric acid in dioxane (Aldrich, Buchs, Switzerland) (5 mL, 20 mmol) and the mixture stirred at 50 to 60° C. for 1 hour. The resulting suspension is diluted with 75 mL of methanol and stirred for 1 additional hour under reflux after which the mixture is cooled and the solvent evaporated. The residue is dissolved in diluted hydrochloric acid and washed with ethyl acetate. The aqueous phase is treated with solid potassium carbonate until basic and evaporated. The residue which contains inorganic salts is purified by flash chromatography using dichloromethane/methanol 7:3 containing 1% conc. ammonia. Pure fractions were taken up in ethyl acetate, washed with water and brine, dried with sodium sulfate and evaporated to give the title compound as a solid; m.p. 240-242° C.; MS-ES+: (M+H)+=413; TLC Rf(dichloromethane/methanol 7:3 containing 1% conc. ammonia) 0.35; HPLC tR=6.86 min.

Workup

  1. stirringstirred for 1 additional hour
  2. temperatureunder reflux after which the mixture
  3. temperatureis cooled
  4. customthe solvent evaporated
  5. dissolutionThe residue is dissolved in diluted hydrochloric acid
  6. washwashed with ethyl acetate
  7. additionThe aqueous phase is treated with solid potassium carbonate until basic and
  8. customevaporated
  9. customis purified by flash chromatography
  10. washwashed with water and brine
  11. dry with materialdried with sodium sulfate
  12. customevaporated

Sources & evidence

ORD record
ord-945d69409ef64c2ab77ead963c2f4839
Source dataset
uspto-grants-2008_01
Patent number
US07323469B2

Reaction notes

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