Sodium Carbonate → tert-butyl 4-(5-(4-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methylcarbamoyl)-1-isopropyl-3-methyl-1H-indazol-6-yl)pyridin-2-yl)piperazine-1-carboxylate

HRID 85491Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 85491
Br[C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])=[O:16])[C:5]2[C:6]([CH3:14])=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:36]2[CH:37]=[CH:38][C:39]([N:42]3[CH2:47][CH2:46][N:45]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:44][CH2:43]3)=[N:40][CH:41]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.O.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>[CH3:25][C:24]1[CH:23]=[C:22]([CH3:26])[NH:21][C:20](=[O:27])[C:19]=1[CH2:18][NH:17][C:15]([C:4]1[CH:3]=[C:2]([C:36]2[CH:37]=[CH:38][C:39]([N:42]3[CH2:47][CH2:46][N:45]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:44][CH2:43]3)=[N:40][CH:41]=2)[CH:10]=[C:9]2[C:5]=1[C:6]([CH3:14])=[N:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[O:16]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 16217947Tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylateHCID 545962226-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide

Produkt 1

HCID 67468774tert-butyl 4-(5-(4-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methylcarbamoyl)-1-isopropyl-3-methyl-1H-indazol-6-yl)pyridin-2-yl)piperazine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a stirred solution of 6-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide (400 mg, 0.928 mmol) in DMF (20 mL) was added tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylate (397 mg, 1.02 mmol) followed by sodium carbonate (246 mg, 2.32 mmol) dissolved in water (4 mL) and degassed with argon for 30 min. PdCl2(PPh3)2 (65 mg, 0.092 mmol) was added and the mixture again degassed with argon for 10 min. The reaction mixture was stirred at 100° C. for 3 h. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (3×150 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated to afford the crude product (650 mg). The crude compound was purified by silica gel chromatography (eluent: 0-10% MeOH: DCM). The product was triturated with diethyl ether (150 mL) to afford the title compound as an off white solid (270 mg, 47%). 1H NMR (DMSO-d6, 400 MHz): δ 1.498 (s, 9H), 1.560 (d, J=6.4 Hz, 6H), 2.128 (s, 3H), 2.413 (s, 3H), 2.526 (s, 3H), 3.579 (s, 8H), 4.610 (d, J=5.6 Hz, 2H), 4.760-4.824 (m, 1H), 5.907 (s, 1H), 6.70 (d, J=8.8 Hz, 1H), 7.311-7.346 (m, 2H), 7.454 (s, 1H), 7.735 (d, J=8.8 Hz, 1H), 8.463 (s, 1H), 10.991 (brs, 1H). LCMS (ES+): 614.25.

Aufarbeitung

  1. customdegassed with argon for 30 min
  2. customthe mixture again degassed with argon for 10 min
  3. additionThe reaction mixture was diluted with water (100 mL)
  4. extractionextracted with ethyl acetate (3×150 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford the crude product (650 mg)
  9. customThe crude compound was purified by silica gel chromatography (eluent: 0-10% MeOH: DCM)
  10. customThe product was triturated with diethyl ether (150 mL)

Quellen und Nachweise

ORD-Eintrag
ord-3d6c31474a23444888adbe792250a99a
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846935B2

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