2-Methyl-2-thiopseudourea → HCID 178473458, Verbindung

HRID 12257

Reaktionsgleichung

Reaktionsgleichung von HRID 12257
CS[C:3](=[NH:5])[NH2:4].Cl[C:7]([O:9][CH2:10][CH3:11])=[O:8].[OH-].[Na+].N[C:15]1[C:20]([NH2:21])=[CH:19][C:18]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:17][C:16]=1[C:28](=[O:31])[CH2:29][CH3:30]>O.CCOC(C)=O.CC(O)=O>[CH2:10]([O:9][C:7](=[O:8])[NH:4][C:3]1[NH:5][C:15]2[C:16]([C:28](=[O:31])[CH2:29][CH3:30])=[CH:17][C:18]([C:22]3[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=3)=[CH:19][C:20]=2[N:21]=1)[CH3:11]

Komponenten

8

Edukt 4

HCID 51422-Methyl-2-thiopseudoureaHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 179849121-(2,3-Diamino-5-pyridin-3-yl-phenyl)-propan-1-one

Produkt 1

HCID 178473458HCID 178473458, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittel3×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a mixture of 2-methyl-2-thiopseudourea (109 mg, 0.39 mmol) and ethyl chloroformate (75 μL, 0.78 mmol) in water (2 mL) at 5° C. was added over 40 minutes a 6N aqueous NaOH solution until pH stabilized to 8. The pH was then adjusted to 5 with glacial AcOH. A suspension of 1-(2,3-diamino-5-pyridin-3-yl-phenyl)-propan-1-one (0.30 mmol) in water (5 mL) was subsequently added to the reaction mixture. The reaction was heated at 90° C. for 18 hours, cooled to ambient temperature, and diluted with water (10 mL) and EtOAc (20 mL). The phases were separated and the aqueous layer extracted with EtOAc (3×). The combined organic extracts were washed with brine, dried (MgSO4), filtered, and the filtrate concentrated in vacuo. The crude residue was taken up in DMSO, purified by preparative HPLC, and by flash column chromatography (SiO2; CH2Cl2:MeOH, 1:0 to 19:1). The residue was then converted to the bis-HCl salt to afford the title compound as an off white solid (5.0 mg): HPLC (10 to 90% CH3CN, 8 min.): Rt=3.90 minutes; 1H NMR (CD3OD, 500 MHz) δ 9.39 (d, 1H), 9.07 (d, 1H), 8.93 (d, 1H), 8.48 (d, 1H), 8.28 (d, 1H), 8.25 (dd, 1H), 4.46 (q, 2H), 3.35 (q, 2H), 1.43 (t, 3H), 1.29 (t, 3H); MS (ES+) m/z (M++1) 339.1.

Aufarbeitung

  1. additionwas subsequently added to the reaction mixture
  2. temperaturecooled to ambient temperature
  3. customThe phases were separated
  4. extractionthe aqueous layer extracted with EtOAc (3×)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated in vacuo
  9. custompurified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-7c5490cbc6894f5eace522a61c214842
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727992B2

Verknüpfte Notizen

Wird geladen…