2,5-Diamino-4,6-dichloropyrimidine → (R)-6-chloro-N4-(8-fluorochroman-4-yl)pyrimidine-2,4,5-triamine

HRID 600419Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 600419
[NH2:1][C:2]1[N:7]=[C:6](Cl)[C:5]([NH2:9])=[C:4]([Cl:10])[N:3]=1.Cl.[F:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][CH2:20][CH2:19][C@H:18]2[NH2:23].C(=O)(O)[O-].[Na+]>C(O)CCC>[Cl:10][C:4]1[N:3]=[C:2]([NH2:1])[N:7]=[C:6]([NH:23][C@H:18]2[C:17]3[C:22](=[C:13]([F:12])[CH:14]=[CH:15][CH:16]=3)[O:21][CH2:20][CH2:19]2)[C:5]=1[NH2:9]

Komponenten

5

Edukt 3

HCID 3010392,5-Diamino-4,6-dichloropyrimidineHCID 516892Sodium BicarbonateHCID 52911303(R)-8-fluorochroman-4-amine hydrochloride

Produkt 1

HCID 57612657(R)-6-chloro-N4-(8-fluorochroman-4-yl)pyrimidine-2,4,5-triamineAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 2631-ButanolLösungsmittel

Versuchsvorschrift

2,5-diamino-4,6-dichloropyrimidine (1.5 g, 8.37 mmol), (R)-8-fluorochroman-4-amine hydrochloride (see preparation below) (1.7 g, 8.37 mmol, 1 equiv.), sodium bicarbonate (2.46 g, 29.3 mmol, 3.5 equiv.) and 1-butanol (30 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, elution with 1/1 ethyl acetate/methylene chloride) to give 2.01 g (78% yield) of the desired product as a yellow solid. 1H NMR (300 MHz, CD3OD) δ, ppm: 6.97-6.86 (m, 2H), 6.77-6.72 (m, 1H), 5.36 (m, 1H), 4.25 (m, 2H), 2.10 (m, 2H); MS (EI) m/z 310.1 (MH)+.

Aufarbeitung

  1. customthe solvent was removed in vacuo
  2. customThe residue was purified by flash chromatography (silica gel, elution with 1/1 ethyl acetate/methylene chloride)

Quellen und Nachweise

ORD-Eintrag
ord-93d9fe9dd8c9474f894a18719455f2ca
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902187B2

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