1,4-Dioxane → 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-((dimethylamino)methyl)phenyl)-1H-indazole-4-carboxamide

HRID 1476431Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1476431
Br[C:2]1[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]2[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])=[O:17])[C:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.[CH3:29][N:30]([CH3:47])[CH2:31][C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][CH:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[CH:11]1([N:8]2[C:9]3[CH:10]=[C:2]([C:35]4[CH:36]=[CH:37][C:32]([CH2:31][N:30]([CH3:47])[CH3:29])=[CH:33][CH:34]=4)[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]4[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=4[CH3:26])=[O:17])[C:5]=3[CH:6]=[N:7]2)[CH2:15][CH2:14][CH2:13][CH2:12]1

Komponenten

8

Edukt 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 34604594-((N,N-Dimethylamino)methyl)phenylboronic acid pinacol esterHCID 545970746-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1H-indazole-4-carboxamide

Produkt 1

HCID 545972301-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-((dimethylamino)methyl)phenyl)-1H-indazole-4-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a sealed tube were added 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (0.10 g, 0.226 mmol), N,N-dimethyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanamine (0.081 g, 0.271 mmol), and potassium phosphate (tribasic) (0.192 g, 0.902 mmol) followed by 1,4-Dioxane (2.0 mL) and water (0.5 mL). The suspension was stirred with degassing under N2 for 10 min, followed by addition of PdCl2(dppf)-CH2Cl2 adduct (0.018 g, 0.023 mmol). The reaction vessel was sealed and stirred with heating at 100° C. (heat block) for 2 h. The contents were allowed to stir with cooling to RT overnight. The mixture was diluted with EtOAc followed by addition of silica gel. The mixture was concentrated in vacuo and the obtained solid purified by silica gel chromatography (dry loaded, eluent: 8-95% gradient of chloroform (containing 10% 2M Ammonia in Methanol) and DCM. The collected product was concentrated from DCM/MTBE and then dried in vacuum oven for 16 h. The title compound was collected as an off-white solid (45 mg, 39%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.65-1.76 (m, 2H), 1.83-1.94 (m, 2H), 1.97-2.07 (m, 2H), 2.09-2.19 (m, 11H), 2.21 (s, 3H), 3.44 (s, 2H), 4.39 (d, J=4.80 Hz, 2H), 5.34 (quin, J=7.14 Hz, 1H), 5.88 (s, 1H), 7.41 (m, J=8.34 Hz, 2H), 7.81 (m, J=8.08 Hz, 2H), 7.87 (d, J=1.01 Hz, 1H), 8.12 (s, 1H), 8.36 (s, 1H), 8.65 (t, J=4.93 Hz, 1H), 11.53 (s, 1H); LC-MS (ES) m/z=498.3 [M+H]+

Aufarbeitung

  1. customwith degassing under N2 for 10 min
  2. customThe reaction vessel was sealed
  3. stirringstirred
  4. temperature(heat block) for 2 h
  5. stirringto stir
  6. temperaturewith cooling to RT overnight
  7. additionfollowed by addition of silica gel
  8. concentrationThe mixture was concentrated in vacuo
  9. customthe obtained solid purified by silica gel chromatography (
  10. customdry
  11. concentrationThe collected product was concentrated from DCM/MTBE
  12. customdried in vacuum oven for 16 h
  13. customThe title compound was collected as an off-white solid (45 mg, 39%)

Quellen und Nachweise

ORD-Eintrag
ord-4c0abd0545d946f099b556c3a0dcaa34
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09018382B2

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