Phosgene → HCID 23630278, Verbindung

HRID 2066684

Reaktionsgleichung

Reaktionsgleichung von HRID 2066684
C(Cl)(Cl)=O.[Cl:5][C:6]1[C:12]([O:13][CH3:14])=[CH:11][C:10]([O:15][CH3:16])=[C:9]([Cl:17])[C:7]=1[NH2:8].[N-:18]=[C:19]=[O:20].[N:21]1([CH2:27][CH2:28][O:29][C:30]2[CH:35]=[CH:34][C:33]([NH:36][C:37]3[CH:42]=[C:41](N)[N:40]=[CH:39][N:38]=3)=[CH:32][CH:31]=2)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C([O-])(O)=O.[Na+]>O1CCOCC1.CN1C(=O)CCC1.C(Cl)Cl>[Cl:5][C:6]1[C:12]([O:13][CH3:14])=[CH:11][C:10]([O:15][CH3:16])=[C:9]([Cl:17])[C:7]=1[NH:8][C:19]([NH:18][C:41]1[CH:42]=[C:37]([NH:36][C:33]2[CH:34]=[CH:35][C:30]([O:29][CH2:28][CH2:27][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:31][CH:32]=2)[N:38]=[CH:39][N:40]=1)=[O:20]

Komponenten

9

Edukt 5

HCID 6371PhosgeneHCID 105034IsocyanateHCID 516892Sodium BicarbonateHCID 594862532,6-Dichloro-3,5-dimethoxyanilineHCID 59864576N-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-pyrimidine-4,6-diamine

Produkt 1

HCID 23630278HCID 23630278, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6344DichloromethaneLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

Phosgene (20% in toluene, 0.8 mL, 1.58 mmol, 2.4 equiv) is added to a solution of 2,6-dichloro-3,5-dimethoxyaniline (175 mg, 0.79 mmol, 1.2 equiv) in dioxane (2.5 mL), under an argon atmosphere. The mixture is heated to reflux, stirred for 1 h, allowed to cool to RT, and concentrated in vacuo. The resulting isocyanate is added to a solution of N-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-pyrimidine-4,6-diamine (208.5 mg, 0.66 mmol) in NMP (2 mL), at 75° C. and under an argon atmosphere. The reaction mixture is stirred at 75° C. for 2 h, allowed to cool to RT, and is then diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated and extracted with DCM. The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 96:4), followed by trituration of the resulting material in MeOH, affords the title compound as a white solid: ESI-MS: 562.9/564.9 [MH]+; tR=2.99 min (purity: 100%, system 1); TLC: Rf=0.36 (DCM/MeOH+1% NH3aq, 93:7).

Aufarbeitung

  1. temperatureThe mixture is heated
  2. temperatureto reflux
  3. concentrationconcentrated in vacuo
  4. stirringThe reaction mixture is stirred at 75° C. for 2 h
  5. temperatureto cool to RT
  6. customThe aqueous layer is separated
  7. extractionextracted with DCM
  8. washThe organic phase is washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 96:4)

Quellen und Nachweise

ORD-Eintrag
ord-55e3d22c6fc14225b5fe84a81bbb8568
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08293746B2

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