Reaktion #79810

Reaktionsgleichung

3-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentan-1-ol

N-methylpiperazine

sodium triacetoxyborohydride

acetic acid

N-methylpiperazine

acetic acid

N-methylpiperazine

sodium triacetoxyborohydride

acetic acid

sodium triacetoxyborohydride

→

7-[3-(4-methylpiperazino) cyclopentyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tri-maleate

Lösungsmittel

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Filtrationfiltered
2. 2
   workup.ADDITIONfresh manganese dioxide (8 g) added to the filtrate
3. 3
   Filtrationthe mixture was filtered
4. 4
   workup.WAITtr 4.38 minutes
5. 5
   workup.STIRRINGthe mixture stirred for 17 hours
6. 6
   workup.STIRRINGstirring for 3 days
7. 7
   Sonstigegave a mixture which
8. 8
   Sonstigewas evaporated under reduced pressure
9. 9
   workup.ADDITIONThe residue was treated with water (200 ml) and 6M -hydrochloric acid (50 ml)
10. 10
    Waschenthen washed with ethyl acetate (discarded)
11. 11
    ExtraktionThe mixture was extracted with ethyl acetate
12. 12
    Trocknenthe extract dried (sodium sulphate)
13. 13
    Sonstigethen purified by flash chromatography in 9:1 ethyl acetate
14. 14
    Sonstigeethanol to remove impurities
15. 15
    Waschenethanol:triethylamine to elute the product
16. 16
    SonstigeSolvent was removed under reduced pressure
17. 17
    workup.DISSOLUTIONthe residue dissolved in ethyl acetate
18. 18
    workup.ADDITIONtreated with a solution of maleic acid in ethyl acetate

Vorschrift

3-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentan-1-ol (2.14 g, 0.0055 mol) in 11 dichloromethane was stirred with 12 g active manganese dioxide for 5 hours, filtered and fresh manganese dioxide (8 g) added to the filtrate. After stirring for a further 17 hours, the mixture was filtered and used directly. HPLC/MS showed starting material and 3-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-cyclopentanone 62.7% tr 4.38 minutes. The dichloromethane solution was stirred with 1.0 g N-methylpiperazine (0.01 mol) and acetic acid (0.6 g, 0.01 mol) for 15 minutes then sodium triacetoxyborohydride (0.89 g, 0.0042 mol) was added. After 2 hours 1.0 g N-methylpiperazine, 0.6 g acetic acid and 0.89 g sodium triacetoxyborohydride was added and the mixture stirred for 17 hours. Further addition of 2.0 g N-methylpiperazine, 1.2 g acetic acid and 1.2 g sodium triacetoxyborohydride and stirring for 3 days gave a mixture which was evaporated under reduced pressure. The residue was treated with water (200 ml) and 6M -hydrochloric acid (50 ml) then washed with ethyl acetate (discarded) and basified with excess aqueous ammonia. The mixture was extracted with ethyl acetate and the extract dried (sodium sulphate) then purified by flash chromatography in 9:1 ethyl acetate: ethanol to remove impurities followed by 8:1:1 ethyl acetate:ethanol:triethylamine to elute the product. Solvent was removed under reduced pressure, the residue dissolved in ethyl acetate and treated with a solution of maleic acid in ethyl acetate giving 7-[3-(4-methylpiperazino) cyclopentyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tri-maleate (444395) as a 1.4 solvate with ethyl acetate after drying at 80° C. under reduced pressure (0.95 g, 0.001 mol) m.pt. 168-170° C. (decomposes).

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