Diisopropylethylamine → 1-[4-[2-(difluoromethyl)-4-methoxybenzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]-N-methylpiperidine-4-sulfonamide

HRID 1256564Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1256564
[CH3:1][NH:2][S:3]([CH:6]1[CH2:11][CH2:10][N:9]([C:12](OCC2C=CC=CC=2)=O)[CH2:8][CH2:7]1)(=[O:5])=[O:4].ClC1[N:28]=[C:27]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[N:26]=[C:25]([N:35]2[C:39]3[CH:40]=[CH:41][CH:42]=[C:43]([O:44][CH3:45])[C:38]=3[N:37]=[C:36]2[CH:46]([F:48])[F:47])[N:24]=1.CCN(C(C)C)C(C)C>CO.C1COCC1.[Pd]>[F:48][CH:46]([F:47])[C:36]1[N:35]([C:25]2[N:26]=[C:27]([N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[N:28]=[C:12]([N:9]3[CH2:8][CH2:7][CH:6]([S:3]([NH:2][CH3:1])(=[O:4])=[O:5])[CH2:11][CH2:10]3)[N:24]=2)[C:39]2[CH:40]=[CH:41][CH:42]=[C:43]([O:44][CH3:45])[C:38]=2[N:37]=1

Komponenten

7

Edukt 3

HCID 81531DiisopropylethylamineHCID 534881021-[4-Chloro-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 66698101benzyl 4-(N-methylsulfamoyl)piperidine-1-carboxylate

Produkt 1

HCID 469175751-[4-[2-(difluoromethyl)-4-methoxybenzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]-N-methylpiperidine-4-sulfonamideAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

The above carbamate was hydrogenated over 5% Pd on carbon in MeOH. After removal of the solvent, the residue was combined with 0.19 g (0.48 mmol) 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (Example 2) and DIPEA in THF. The mixture was heated under reflux for 30 min and the solvent was concentrated. After dilution with water, the resulting solid was collected and dried. Chromatography on alumina, eluting with CH2Cl2/EtOAc (9:1), gave 0.127 g (39% yield) of 1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-N-methyl-4-piperidinesulfonamide: mp (MeOH) 261-263° C.; 1H NMR (CDCl3) δ 7.87 (dd, J=8.4, 0.6 Hz, 1H), 7.46 (t, JHF=53.6 Hz, 1H), 7.35 (t, J=8.0 Hz, 1H), 6.82 (d, J=7.7 Hz, 1H), 4.93 (br d, J=13.5 Hz, 2H), 4.05 (s, 3H), 4.02 (q, J=5.3 Hz, 1H), 3.88 (m, 4H), 3.78 (m, 4H), 3.22 (tt, J=11.8, 3.7 Hz, 1H), 3.00 (m, 2H), 2.86 (d, J=5.3 Hz, 3H), 2.24 (br d, J=12.0 Hz, 2H), 1.85 (dq, J=12.5, 4.4 Hz, 2H); Anal. Calcd. for C22H28F2N8O4S: C, 49.1; H, 5.2; N, 20.8. Found: C, 49.2; H, 5.3; N, 21.0%.

Aufarbeitung

  1. customAfter removal of the solvent
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for 30 min
  4. concentrationthe solvent was concentrated
  5. customAfter dilution with water, the resulting solid was collected
  6. customdried
  7. washChromatography on alumina, eluting with CH2Cl2/EtOAc (9:1)

Quellen und Nachweise

ORD-Eintrag
ord-b2a2fef341ac416fb540cde97b2688f8
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08461158B2

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