Trifluoroacetic acid → 1-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-3-[4-(5-morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidin-1-yl]-propan-2-ol

HRID 586734Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 586734
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:22]3[C:17](=[CH:18][N:19]=[C:20]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[CH:21]=3)[NH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[CH3:36][S:37]([N:40]1[CH2:45][CH2:44][C:43]2[N:46]([CH2:59][CH:60]3[CH2:62][O:61]3)[N:47]=[C:48]([C:49]3[CH:54]=[CH:53][C:52]([C:55]([F:58])([F:57])[F:56])=[CH:51][CH:50]=3)[C:42]=2[CH2:41]1)(=[O:39])=[O:38]>C(Cl)Cl>[NH3:8].[CH3:36][S:37]([N:40]1[CH2:45][CH2:44][C:43]2[N:46]([CH2:59][CH:60]([OH:61])[CH2:62][N:8]3[CH2:9][CH2:10][CH:11]([C:14]4[C:22]5[C:17](=[CH:18][N:19]=[C:20]([N:23]6[CH2:24][CH2:25][O:26][CH2:27][CH2:28]6)[CH:21]=5)[NH:16][CH:15]=4)[CH2:12][CH2:13]3)[N:47]=[C:48]([C:49]3[CH:50]=[CH:51][C:52]([C:55]([F:56])([F:57])[F:58])=[CH:53][CH:54]=3)[C:42]=2[CH2:41]1)(=[O:39])=[O:38]

Komponenten

6

Edukt 3

HCID 6422Trifluoroacetic acidHCID 120720315-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridineHCID 691828124-(5-Morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidine-1-carboxylic acid tert-butyl ester

Produkt 2

HCID 222AmmoniaHCID 101466241-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-3-[4-(5-morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidin-1-yl]-propan-2-olAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

4-(5-Morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidine-1-carboxylic acid tert-butyl ester (180 mg, 0.47 mmol) was dissolved in 3.0 mL of CH2Cl2 and treated with 2.5 mL of trifluoroacetic acid. The reaction mixture was stirred at 25° C. for 1 h before all volatiles were removed. The solid was dissolved in MeOH (20 mL) and neutralized with DOWEX 550A OH anion exchange resin to pH 8. The resin was then filtered off and MeOH was removed under reduced pressure. The residue was dissolved in 2.5 mL of iPrOH and treated with 187 mg (0.47 mmol, 1 eq) of 5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine. The reaction was stirred at 85° C. for 3 h before solvent was removed. Column chromatography (silica, 5-10% MeOH/CH2Cl2 then 5-10% (2 N NH3 in MeOH)/CH2Cl2) provided 97 mg (30%) of the title compound. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.25. MS (electrospray): exact mass calculated for C33H40F3N7O4S, 687.28; m/z found, 688.3 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.47 (br s, 1H), 8.44 (d, J=1.0 Hz, 1H), 7.70 and 7.65 (AB pattern, J=8.4 Hz, 4H), 7.03 (d, J=2.1 Hz, 1H), 6.76 (s, 1H), 4.58-4.50 (m, 2H), 4.21-4.00 (m, 3H), 3.90 (t, J=4.5 Hz, 4H), 3.72-3.58 (m, 2H), 3.40 (t, J=4.5 Hz, 4H), 3.10-2.85 (m, 4H), 2.88 (s, 3H), 2.80-2.70 (m, 1H), 2.52-2.41 (m, 3H), 2.20-2.00 (m, 3H), 1.80-1.60 (m, 2H).

Aufarbeitung

  1. customwere removed
  2. dissolutionThe solid was dissolved in MeOH (20 mL)
  3. filtrationThe resin was then filtered off
  4. customMeOH was removed under reduced pressure
  5. dissolutionThe residue was dissolved in 2.5 mL of iPrOH
  6. stirringThe reaction was stirred at 85° C. for 3 h before solvent
  7. customwas removed

Quellen und Nachweise

ORD-Eintrag
ord-05ad0ade24c045d9b09b25794d333637
Quelldatensatz
uspto-grants-2005_08
Patentnummer
US06936603B2

Notizen zur Reaktion

Wird geladen…