2,5-Diamino-4,6-dichloropyrimidine → 6-chloro-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4,5-triamine

HRID 600398Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 600398
[NH2:1][C:2]1[N:7]=[C:6](Cl)[C:5]([NH2:9])=[C:4]([Cl:10])[N:3]=1.[NH2:11][CH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C(=O)(O)[O-].[Na+]>C(O)CCC>[Cl:10][C:4]1[N:3]=[C:2]([NH2:1])[N:7]=[C:6]([NH:11][CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:5]=1[NH2:9]

Komponenten

5

Edukt 3

HCID 3010392,5-Diamino-4,6-dichloropyrimidineHCID 4192234-AminotetrahydropyranHCID 516892Sodium Bicarbonate

Produkt 1

HCID 576126486-chloro-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4,5-triamineAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 2631-ButanolLösungsmittel

Versuchsvorschrift

2,5-diamino-4,6-dichloropyrimidine (6 g, 33.5 mmol), 4-aminotetrahydropyran (3.39 g, 33.5 mmol, 1 equiv.), sodium bicarbonate (9.85 g, 117.2 mmol, 3.5 equiv.) and 1-butanol (120 mL) were heated together at 150° C. in a sealed tube. After 3 days, when the reaction appeared to be complete (by HPLC), the reaction mixture was cooled to room temperature and the solvent was removed in vacuo. The residue was purified by flash chromatography (silica gel, gradual elution with 95/5 methylene chloride/methanol to 90/10 methylene chloride/methanol) to give 7.1 g (87% yield) of the desired product as a pink solid. In an alternative procedure, water (300 mL) was added to the residue (before chromatographic purification) and the mixture stirred for 30 min at room temperature. Filtration under vacuum, thorough washing of the precipitate with water, followed by thorough drying of the pink solid in vacuum oven at 60° C., provided high purity desired product in 78% yield. 1H NMR (300 MHz, CD3OD) δ, ppm: 4.21-4.12 (m, 1H), 4.01-3.96 (m, 2H), 3.53 (td, J=11.7, 2.2 Hz, 2H), 2.01-1.96 (m, 2H), 1.60 (tdd, J=12.1, 11.7, 4.6 Hz, 2H); MS (EI) m/z 244.3 (MH)+.

Aufarbeitung

  1. customthe solvent was removed in vacuo
  2. customThe residue was purified by flash chromatography (silica gel, gradual elution with 95/5 methylene chloride/methanol to 90/10 methylene chloride/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-ba506216d87b479fab4e29a569d976d2
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902187B2

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