1H-Purine-2,6-dione, 7-(2-(ethyl(2-hydroxyethyl)amino)ethyl)-3,7-dihydro-1,3-dimethyl-8-(phenylmethyl)-, hydrochloride (1:1) → 1-[6-(Pyridin-3-ylmethoxy)-pyridin-2-yl]-piperazine

HRID 1743283Notes

Reaction equation

HRID 1743283 reaction equation
Cl.[CH3:2][CH2:3][O:4][CH2:5][CH3:6].CCN(CCO)C[CH2:11][N:12]1[C:16]2[C:17]([N:19]([CH3:24])C(N(C)C=2[N:14]=[C:13]1[CH2:25][C:26]1C=CC=CC=1)=O)=O.Cl>CCOCC>[N:12]1[CH:13]=[CH:25][CH:26]=[C:2]([CH2:3][O:4][C:5]2[N:14]=[C:13]([N:12]3[CH2:11][CH2:24][NH:19][CH2:17][CH2:16]3)[CH:25]=[CH:26][CH:6]=2)[CH:11]=1

Participants

4

Reactant 2

HCID 685491H-Purine-2,6-dione, 7-(2-(ethyl(2-hydroxyethyl)amino)ethyl)-3,7-dihydro-1,3-dimethyl-8-(phenylmethyl)-, hydrochloride (1:1)HCID 10953452Ether hydrochloride

Product 1

HCID 98351631-[6-(Pyridin-3-ylmethoxy)-pyridin-2-yl]-piperazine

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of 2-bromo-6-(pyridin-3-ylmethoxy)-pyridin-hydrochloride prepared as above (25.07 g, 94.6 mmol) was suspended in 275 mL of dry dioxane and then 65.06 g (756.5 mmol, 8 equiv.) of piperazine and 14.19 g (94.6 mmol) of NaI were added. The reaction mixture was then heated slowly to reflux under an atmosphere of dry N2. After about 1 h, the solids in the reaction mixture went partially into solution. Reflux was continued for 48 h at which time the reaction mixture was cooled and taken up in cold water, giving a pale yellow solution. This was extracted four times with ethyl acetate and the combined extracts were backwashed once with water and washed with saturated NaCl solution. The organic solution was dried with MgSO4 and the solvent was evaporated to give 20.7 g of pale yellow oil. This oil was dissolved in 500 mL of dry ether and stirred rapidly while 75 mL of 1 M HCl/ether solution was added dropwise (the mixture was seed with a small amount of mono-HCL salt prepared earlier by the same procedure on smaller scale). The HCl salt crystallized and was granulated overnight at room temperature under N2 atmosphere. The crystalline salt was filtered off and washed with dry ether and dried in a stream of dry N2 and residual ether was removed by pumping in high vacuum for 5 h to give 21.67 g (75%) of off white solid, m.p.=141–143° C.

Workup

  1. additionwas added dropwise (the mixture
  2. customprepared earlier by the same procedure on smaller scale)
  3. customThe HCl salt crystallized
  4. filtrationThe crystalline salt was filtered off
  5. washwashed with dry ether
  6. dry with materialdried in a stream of dry N2 and residual ether
  7. customwas removed
  8. waitby pumping in high vacuum for 5 h
  9. customto give 21.67 g (75%) of off white solid, m.p.=141–143° C.

Sources & evidence

ORD record
ord-02a9738038ca4bd5a55c2d8a700e50b7
Source dataset
uspto-grants-2006_03
Patent number
US07009051B2

Reaction notes

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