5-Bromopyridine-2-carboxamide → HCID 59619817, Verbindung

HRID 445675

Reaktionsgleichung

Reaktionsgleichung von HRID 445675
[CH:1]([N:4]1[CH:8]=[C:7]([N:9]2[C:21]3[C:20]4[CH:19]=[C:18](B5OC(C)(C)C(C)(C)O5)[CH:17]=[CH:16][C:15]=4[N:14]=[CH:13][C:12]=3[N:11]([CH3:31])[C:10]2=[O:32])[C:6]([CH3:33])=[N:5]1)([CH3:3])[CH3:2].Br[C:35]1[CH:36]=[CH:37][C:38]([C:41]([NH2:43])=[O:42])=[N:39][CH:40]=1>CN(C=O)C.C([O-])([O-])=O.[K+].[K+].CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:1]([N:4]1[CH:8]=[C:7]([N:9]2[C:21]3[C:20]4[CH:19]=[C:18]([C:35]5[CH:36]=[CH:37][C:38]([C:41]([NH2:43])=[O:42])=[N:39][CH:40]=5)[CH:17]=[CH:16][C:15]=4[N:14]=[CH:13][C:12]=3[N:11]([CH3:31])[C:10]2=[O:32])[C:6]([CH3:33])=[N:5]1)([CH3:3])[CH3:2]

Komponenten

7

Edukt 2

HCID 7351515-Bromopyridine-2-carboxamideHCID 596197411-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-3-methyl-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

Produkt 1

HCID 59619817HCID 59619817, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolKatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 11430Potassium CarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

A mixture of 1-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-3-methyl-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Stage 112.1.1, 34 mg, 0.075 mmol), 5-bromo-pyridine-2-carboxylic acid amide (Combi-Blocks, San Diego, USA, 20 mg, 0.099 mmol), and PdCl2(PPh3)2 (3.5 mg, 0.005 mmol) in DMF (0.9 ml) and 1 M aqueous K2CO3 (0.187 ml) was stirred under argon at 105° C. for 2.5 h. The RM was cooled to rt. The mixture was diluted with MeOH+3 drops TFA and purified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 97:3 to 55:45). The fractions containing product were collected together and basified with NaHCO3 (0.3 g), before being concentrated. The resulting layer was extracted with DCM, washed with brine, dried over Na2SO4, filtered and evaporated to dryness to give the title compound as a white solid. (HPLC: tR 2.44 min (Method A); M+H=442 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 9.00 (s, 1H), 8.75-8.69 (m, 1H), 8.24-8.19 (m, 1H), 8.18-8.07 (m, 2H), 8.07-7.98 (m, 3H), 7.75-7.67 (m, 1H), 7.61-7.56 (m, 1H), 4.61-4.48 (m, 1H), 3.58 (s, 3H), 1.97 (s, 3H), 1.45 (s, 3H), 1.43 (s, 3H))

Aufarbeitung

  1. temperatureThe RM was cooled to rt
  2. custompurified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 97:3 to 55:45)
  3. additionThe fractions containing product
  4. customwere collected together
  5. concentrationbefore being concentrated
  6. extractionThe resulting layer was extracted with DCM
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-81d57a7faa5247fcaa029ae92de89cb6
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476294B2

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