Diisopropylethylamine → (R)-4-amino-N-(1-(4-chlorophenyl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide

HRID 422994Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 422994
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(OC([NH:32][C:33]1([C:48]([OH:50])=O)[CH2:38][CH2:37][N:36]([C:39]2[C:40]3[CH:47]=[CH:46][NH:45][C:41]=3[N:42]=[CH:43][N:44]=2)[CH2:35][CH2:34]1)=O)(C)(C)C.[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([C@H:58]([NH2:60])[CH3:59])=[CH:54][CH:53]=1.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[NH2:32][C:33]1([C:48]([NH:60][C@@H:58]([C:55]2[CH:56]=[CH:57][C:52]([Cl:51])=[CH:53][CH:54]=2)[CH3:59])=[O:50])[CH2:34][CH2:35][N:36]([C:39]2[C:40]3[CH:47]=[CH:46][NH:45][C:41]=3[N:42]=[CH:43][N:44]=2)[CH2:37][CH2:38]1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 1715226(1R)-1-(4-chlorophenyl)ethan-1-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 577503944-((tert-Butoxycarbonyl)amino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid2×

Produkt 1

HCID 57750343(R)-4-amino-N-(1-(4-chlorophenyl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamideAusbeute 52,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.418 g, 1.10 mmol) was added in one portion to 4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 1) (0.361 g, 1 mmol), (R)-1-(4-chlorophenyl)ethanamine (0.156 g, 1.00 mmol) and DIPEA (0.524 mL, 3.00 mmol) in DMA (10 mL) at 25° C. under nitrogen. The resulting solution was stirred at 60° C. for 4 hours. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7N ammonia/MeOH and pure fractions were evaporated to dryness. The crude material was treated with a 10% solution of TFA in DCM (5 mL) and stirred at room temperature. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7N ammonia/MeOH and pure fractions were evaporated to dryness. The crude product was purified by preparative LCMS using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (R)-4-amino-N-(1-(4-chlorophenyl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (0.211 g, 52.9%) as a white solid.

Aufarbeitung

  1. customThe crude product was purified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. customwere evaporated to dryness
  4. additionThe crude material was treated with a 10% solution of TFA in DCM (5 mL)
  5. stirringstirred at room temperature
  6. customThe crude product was purified by ion exchange chromatography
  7. washThe desired product was eluted from the column
  8. customwere evaporated to dryness
  9. customThe crude product was purified by preparative LCMS
  10. additionFractions containing the desired compound
  11. customwere evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-c4c2db0415b64ea9829574acb22e3db3
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101623B2

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