Trifluoroacetic acid → HCID 42602173, Verbindung

HRID 422979Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 422979
FC(F)(F)C(O)=O.[NH2:8][CH2:9][CH:10]([NH:18][C:19]([C:21]1([NH:36]C(=O)OC(C)(C)C)[CH2:26][CH2:25][N:24]([C:27]2[C:28]3[CH:35]=[CH:34][NH:33][C:29]=3[N:30]=[CH:31][N:32]=2)[CH2:23][CH2:22]1)=[O:20])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1>C(Cl)Cl>[NH2:36][C:21]1([C:19]([NH:18][CH:10]([C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)[CH2:9][NH2:8])=[O:20])[CH2:22][CH2:23][N:24]([C:27]2[C:28]3[CH:35]=[CH:34][NH:33][C:29]=3[N:30]=[CH:31][N:32]=2)[CH2:25][CH2:26]1

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 57750411HCID 57750411, Verbindung2×

Produkt 1

HCID 42602173HCID 42602173, VerbindungAusbeute 11,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

Trifluoroacetic acid (3 mL) was added to tert-butyl 4-(2-amino-1-(4-chlorophenyl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (Intermediate 6) (0.514 g) in DCM (100 mL) at 25° C. The resulting solution was stirred at 25° C. for 3 hours. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness. This material was then further purified by flash silica chromatography, elution gradient 0 to 10% methanolic ammonia (7N) in DCM. Pure fractions were evaporated to dryness to afford 4-amino-N-(2-amino-1-(4-chlorophenyl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide as a colourless gum (0.047 g, 11.4%).

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. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  5. additionFractions containing the desired compound
  6. customwere evaporated to dryness
  7. customThis material was then further purified by flash silica chromatography, elution gradient 0 to 10% methanolic ammonia (7N) in DCM
  8. customPure fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-26c3190c82cb4c4cb7266b8316375eba
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101623B2

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