Tetrabutylammonium Fluoride → 7-[1-[(Tert-butoxycarbonylamino)methyl]-2-methyl-propyl]-2-chloro-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid

HRID 72785Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 72785
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:5]([C:19]#[C:20][CH:21]([O:25]CC)[O:22]CC)=[CH:4][N:3]=1.[CH3:28][CH2:29][CH2:30]C[N+](CCCC)(CCCC)CCCC.[F-].OOS([O-])=O.[K+]>C1COCC1.CN(C=O)C.C(OCC)(=O)C.C(O)(=O)C.O.O>[C:14]([O:13][C:12]([NH:11][CH2:10][CH:9]([N:8]1[C:6]2[N:7]=[C:2]([Cl:1])[N:3]=[CH:4][C:5]=2[CH:19]=[C:20]1[C:21]([OH:22])=[O:25])[CH:29]([CH3:30])[CH3:28])=[O:18])([CH3:15])([CH3:16])[CH3:17]

Komponenten

9

Edukt 3

HCID 2724141Tetrabutylammonium FluorideHCID 23707502Potassium hydroxy sulfiteHCID 86695595tert-butyl N-[2-[[2-chloro-5-(3,3-diethoxyprop-1-ynyl)pyrimidin-4-yl]amino]ethyl]carbamate

Produkt 1

HCID 866955947-[1-[(Tert-butoxycarbonylamino)methyl]-2-methyl-propyl]-2-chloro-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×HCID 21899381Acetic acid--water (1/1)Lösungsmittel

Versuchsvorschrift

To a solution tert-butyl N-[2-[[2-chloro-5-(3,3-diethoxyprop-1-ynyl)pyrimidin-4-yl]amino]ethyl]carbamate in THF was added TBAF and the contents refluxed for 3 hrs. Ethyl acetate and water was then added and the organic layer separated, dried with magnesium sulfate and then concentrated under vacuum. To this crude reaction was added acetic acid/water (9:1) and then contents stirred for 12 hrs at room temperature. After concentration under vacuum, sat NaHCO3 and ethyl acetate was then added. The organic layer was separated, dried and then concentrated under vacuum. The crude reaction product thus obtained was dissolved in DMF, oxone was then added and the contents stirred for 3 hrs. After addition of ethyl acetate, the reaction mixture was filtered through CELITE™ and concentrated under vacuum. Column chromatography of the crude product over silica gel using hexane/ethyl acetate (0-100%) afforded 7-[1-[(tert-butoxycarbonylamino)methyl]-2-methyl-propyl]-2-chloro-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid. 1H NMR (600 MHz, DMSO-d6) δ ppm 0.85 (d, J=7.03 Hz, 3H) 0.97 (d, J=6.73 Hz, 3H) 1.52 (s, 9H) 1.99-2.23 (m, 1H) 3.98 (dd, J=14.05, 3.51 Hz, 1H) 4.47-4.71 (m, 2H) 7.47 (s, 1H) 9.17 (s, 1H). LCMS (ESI) 383 (M+H).

Aufarbeitung

  1. temperaturethe contents refluxed for 3 hrs
  2. customthe organic layer separated
  3. dry with materialdried with magnesium sulfate
  4. concentrationconcentrated under vacuum
  5. customTo this crude reaction
  6. concentrationAfter concentration under vacuum
  7. additionwas then added
  8. customThe organic layer was separated
  9. customdried
  10. concentrationconcentrated under vacuum
  11. customThe crude reaction product
  12. customthus obtained
  13. stirringthe contents stirred for 3 hrs
  14. filtrationthe reaction mixture was filtered through CELITE™
  15. concentrationconcentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-93b699e4b2ae45878e4007edf5efb8cc
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829012B2

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