Nitrogen → N-(4-[{4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-4-methyl-3-[(2-oxo-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-6-yl)ethynyl]benzamide

HRID 1255953Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1255953
[CH3:1][P:2]([CH2:5][N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:30])[C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([C:28]#[CH:29])[CH:22]=3)=[CH:15][C:14]=2[C:31]([F:34])([F:33])[F:32])[CH2:8][CH2:7]1)([CH3:4])=[O:3].Br[C:36]1[CH:45]=[N:44][C:43]2[NH:42][C:41](=[O:46])CO[C:38]=2[CH:37]=1.N#N.C(N(CC)C(C)C)(C)C.C[CH2:59][O:60]C(C)=O>[Cu]I.O.CN(C=O)C>[CH3:1][P:2]([CH2:5][N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:30])[C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([C:28]#[C:29][C:36]4[CH:45]=[N:44][C:43]5[NH:42][C:41](=[O:46])[O:60][CH2:59][C:38]=5[CH:37]=4)[CH:22]=3)=[CH:15][C:14]=2[C:31]([F:34])([F:32])[F:33])[CH2:8][CH2:7]1)([CH3:4])=[O:3]

Komponenten

9

Edukt 5

HCID 947NitrogenHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 159259837-bromo-2H,3H,4H-pyrido(3,2-b)(1,4)oxazin-3-oneHCID 86632313N-[4-({4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-3-ethynyl-4-methylbenzamide

Produkt 1

HCID 68911400N-(4-[{4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-4-methyl-3-[(2-oxo-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-6-yl)ethynyl]benzamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

N-[4-({4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-3-(trifluoromethyl)phenyl]-3-ethynyl-4-methylbenzamide (0.22 mmol), 7-bromo-4H-pyrido[3,2-b][1,4]oxazin-3-one (45.8 mg, 0.2 mmol), Pd[(PPh3)]4 (11.6 mg, 0.01 mmol). CuI (2.9 mg, 0.015 mmol) is placed in a vial capped with rubber septa. This vial is subjected to 3 cycles of vacuum-refilling with N2. To this mixture is added anhydrous N,N-diisopropylethylamine (0.1 mL, 0.6 mmol) and DMF (1.0 mL). The resulting solution is stirred at 80° C. for 24 h. After the reaction mixture is cooled, water and EtOAc are added to facilitate the extraction. The combined organic layers are dried over Na2SO4, filtered, and then concentrated on a rotavap and the residue is purified on a silica gel column (eluent: 10% MeOH in CH2Cl2, MeOH is pre-saturated with NH3 gas).

Aufarbeitung

  1. customa vial capped with rubber septa
  2. temperatureAfter the reaction mixture is cooled
  3. extractionthe extraction
  4. dry with materialThe combined organic layers are dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated on a rotavap
  7. customthe residue is purified on a silica gel column (eluent: 10% MeOH in CH2Cl2, MeOH is pre-saturated with NH3 gas)

Quellen und Nachweise

ORD-Eintrag
ord-a0798ba5100a4f8f80f6d01bdd75d486
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08461167B2

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