Hydrochloric Acid → HCID 178457041, Verbindung

HRID 2040670Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2040670
Cl.[Cl:2][C:3]1[C:4]([C:51]([F:54])([F:53])[F:52])=[CH:5][C:6]2[N:10]=[C:9]([CH2:11][CH:12]3[CH2:15][CH:14]([CH2:16][N:17]([CH2:21][C@@H:22]4[C@H:26]5[O:27]C(C)(C)[O:29][C@H:25]5[C@H:24]([N:32]5[C:36]6[N:37]=[CH:38][N:39]=[C:40]([NH2:41])[C:35]=6[CH:34]=[CH:33]5)[CH2:23]4)[CH:18]([CH3:20])[CH3:19])[CH2:13]3)[N:8](COCC[Si](C)(C)C)[C:7]=2[CH:50]=1>CO>[NH2:41][C:40]1[C:35]2[CH:34]=[CH:33][N:32]([C@@H:24]3[CH2:23][C@H:22]([CH2:21][N:17]([CH2:16][CH:14]4[CH2:15][CH:12]([CH2:11][C:9]5[NH:8][C:7]6[CH:50]=[C:3]([Cl:2])[C:4]([C:51]([F:53])([F:52])[F:54])=[CH:5][C:6]=6[N:10]=5)[CH2:13]4)[CH:18]([CH3:20])[CH3:19])[C@@H:26]([OH:27])[C@H:25]3[OH:29])[C:36]=2[N:37]=[CH:38][N:39]=1

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 677763577-[(3aS,4R,6R,6aR)-6-({[(3-{[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutyl)methyl](propan-2-yl)amino]methyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Produkt 1

HCID 178457041HCID 178457041, VerbindungAusbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

12N HCl (1.5 ml) was added slowly to a solution of 7-[(3aS,4R,6R,6aR)-6-({[(3-{[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutyl)methyl](propan-2-yl)amino}methyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (174 mg, 0.22 mmol) in MeOH (1.5 ml) and stirred at 40° C. for 6 h. The reaction was monitored by LCMS, no starting material seen after 2.5 h. The reaction mixture was concentrated in vacuo, then basified with 7N NH3 in MeOH (5 ml). This was then evaporated to dryness. Purification by silica gel column chromatography, eluting with 7N NH3 in MeOH:DCM (1:9) gave the desired product (36 mg, 27%) as a white solid; MS (ESI+) for C29H35ClF3N7O2 m/z 606.30 [M+H]+; HPLC purity 100% (ret. time, 2.59 min); 1H NMR (500 MHz, MOD) δH ppm 0.93-1.09 (6 H, m), 1.41-1.64 (2 H, m), 1.76-2.06 (1 H, m), 2.15-2.65 (9 H, m), 2.65-2.88 (1 H, m), 2.91-3.13 (3 H, m), 3.80-4.09 (1 H, m), 4.19-4.46 (1 H, m), 4.88-4.94 (1 H, m), 6.46-6.77 (1 H, m), 7.19 (1 H, d, J=3.63 Hz), 7.69 (1 H, s), 7.89 (1 H, s), 8.06 (1 H, s)

Aufarbeitung

  1. waitno starting material seen after 2.5 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customThis was then evaporated to dryness
  4. customPurification by silica gel column chromatography
  5. washeluting with 7N NH3 in MeOH:DCM (1:9)

Quellen und Nachweise

ORD-Eintrag
ord-2d3b222d65ee428b8c3acd786610cad9
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08580762B2

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