Sodium Carbonate → 6-(2-chloro-4-methanesulfonyl-phenyl)-8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 1403111Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1403111
[CH2:1]([N:3]1[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)=[CH:16][CH:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=[C:5](B(O)O)[C:4]1=[O:30])[CH3:2].Br[C:32]1[CH:37]=[CH:36][C:35]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH:34][C:33]=1[Cl:42].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(COC)OC.O>[Cl:42][C:33]1[CH:34]=[C:35]([S:38]([CH3:41])(=[O:40])=[O:39])[CH:36]=[CH:37][C:32]=1[C:5]1[C:4](=[O:30])[N:3]([CH2:1][CH3:2])[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:15]=[CH:16][C:17]([N:20]4[CH2:21][CH2:22][N:23]([CH3:26])[CH2:24][CH2:25]4)=[CH:18][CH:19]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 671196488-Ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-boronic acidHCID 679975331-Bromo-2-chloro-4-(methylsulfonyl)benzene

Produkt 1

HCID 546714136-(2-chloro-4-methanesulfonyl-phenyl)-8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-oneAusbeute 37 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 18180031Water 1,2-dimethoxyethaneLösungsmittel

Versuchsvorschrift

8-Ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-boronic acid (5, 100 mg, 0.24 mmol), 1-bromo-2-chloro-4-methylsulfonylbenzene (9, 75 mg, 0.28 mmol), sodium carbonate (80 mg, 0.75 mmol) and Pd(PPh3)4 (30 mg, 0.026 mmol) were mixed under argon in a degassed mixture of dimethoxyethane:water (10:1, 2.5 mL). The resulting suspension was irradiated for 30 min at 120° C. in a microwave reactor. After completion, the reaction mixture was evaporated and the residue was purified by column chromatography using dichloromethane:methanol (100:3) as eluent, The crude product was triturated with isopropyl ether (10 mL) and collected. The title compound (49 mg, 0.088 mmol, 37%) was obtained as a yellow solid. ESMS m/z 553 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.04 (d, J=2.0 Hz, 1H) 7.86 (d, J=8.3 Hz, 1H) 7.69 (dd, J=8.3, 2.0 Hz, 1H) 3.08 (s, 3H).

Aufarbeitung

  1. customThe resulting suspension was irradiated for 30 min at 120° C. in a microwave reactor
  2. customAfter completion, the reaction mixture was evaporated
  3. customthe residue was purified by column chromatography
  4. customThe crude product was triturated with isopropyl ether (10 mL)
  5. customcollected

Quellen und Nachweise

ORD-Eintrag
ord-74cc197d5ac94037888da0cea44e1cfe
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08912203B2

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