Diisopropylethylamine → 1-{4-[(Benzyl-methyl-amino)-methyl]-2-methoxy-phenyl}-3-(5-methyl-pyrazin-2-yl)-urea

HRID 1830785Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1830785
C[C:2]1[N:3]=[CH:4][C:5]([C:8](O)=O)=[N:6][CH:7]=1.C([N:14]([CH:17](C)C)CC)(C)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:27])C=CC=CC=1.[CH2:37]([N:44]([CH2:46][C:47]1[CH:52]=[CH:51][C:50]([NH2:53])=[C:49]([O:54][CH3:55])[CH:48]=1)[CH3:45])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C1(C)C=CC=CC=1.CCOC(C)=O>[CH2:37]([N:44]([CH2:46][C:47]1[CH:52]=[CH:51][C:50]([NH:53][C:17]([NH:14][C:2]2[CH:7]=[N:6][C:5]([CH3:8])=[CH:4][N:3]=2)=[O:27])=[C:49]([O:54][CH3:55])[CH:48]=1)[CH3:45])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 1228315-Methyl-2-pyrazinecarboxylic acidHCID 199401P,P-Diphenylphosphinic azideHCID 220463124-[(Benzyl-methyl-amino)-methyl]-2-methoxy-phenylamine

Produkt 1

HCID 220465131-{4-[(Benzyl-methyl-amino)-methyl]-2-methoxy-phenyl}-3-(5-methyl-pyrazin-2-yl)-ureaAusbeute 40,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

In a 50 mL round bottom flask, 5-methylpyrazine-2-carboxylic acid (250 mg, 1.8 mmol) and diisopropylethylamine (330 μL, 1.9 mmol) in 20 mL toluene, was stirred under a nitrogen atmosphere until the acid dissolved. Diphenylphosphoryl azide (523 mg, 1.9 mmol) was added and the solution was heated to 90° C. After 20 minutes, nitrogen evolution had subsided, and the solution had darkened to a caramel color. The reaction was cooled to 65° C., and 4-[(benzyl-methyl-amino)-methyl]-2-methoxy-phenylamine (486 mg, 1.9 mmol) was added as a solution in 5 mL toluene. The reaction was allowed to stir at 65° C. for 6 h, and was then cooled to room temperature, diluted with 30 mL EtOAc, and washed with 15 mL 5% NH4OH. The aqueous phase was extracted with EtOAc (2×20 mL) and the combined organics were washed with 30 mL brine, dried over MgSO4, filtered, and concentrated. The resulting residue was purified by flash chromatography to give 285 mg (40%) of the desired product, which was further purified by trituration with diethyl ether. Mp=142-143° C. 1H NMR (400 MHz, CDCl3): δ11.33 (s, 1H), 9.51 (s, 1H), 8.41 (s, 1H), 8.27 (d, J=8.61 Hz, 1H), 8.08 (s, 1H), 7.2-7.4 (m, 5H), 6.96 (d, J=7.83 Hz, 1H) 3.97 (s, 3H), 3.53 (s, 4H), 2.53 (s, 3H), 2.22 (s, 1H). 13C NMR (400 MHz, CDCl3): δ153.70, 149.03, 147.48, 147.4, 145.99, 138.73, 137.38, 134.81, 129.19, 128.42, 127.16, 121.89, 119.81, 111.05, 104.49, 94.98, 87.22, 61.81, 56.37, 42.5. MS (APCI-pos)M+1=392.0.

Aufarbeitung

  1. dissolutiondissolved
  2. temperatureThe reaction was cooled to 65° C.
  3. temperaturewas then cooled to room temperature
  4. washwashed with 15 mL 5% NH4OH
  5. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
  6. washthe combined organics were washed with 30 mL brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-ddad2bc15bd346e3bbe0194ead51bd5d
Quelldatensatz
uspto-grants-2006_06
Patentnummer
US07067506B2

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