Reaktion #3580

Reaktionsgleichung

7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine

sodium hydride

7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine

carbamic acid-1,1-dimethylethyl ester

N,N'-Bis(tert-butoxycarbonyl)-N-(ethyl)-S-(ethyl)isothiourea

2.6-lutidine

Trimethylsilyl trifluoromethanesulfonate

sodium bicarbonate

→

title compound

Ausbeute 14.3%

6-(2,6-Dichlorophenyl)-2-(3-diethylamino-propyl-amino)-pyrido[2,3-d]pyrimidin-7-yl-N"-ethyl-guanidine

Ausbeute 14.3%

Lösungsmittel

dichloromethane

DMF

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture was stirred for 18 hours
2. 2
   Waschenwashed with water (2×15 mL)
3. 3
   TrocknenThe organic layer was dried with sodium sulfate
4. 4
   Einengenconcentrated
5. 5
   SonstigeThe resulting oil was purified on silica gel
6. 6
   Wascheneluting with methanol:ethyl acetate:triethylamine (8.5:1.5:0.3)
7. 7
   Sonstigeto afford
8. 8
   workup.STIRRINGthe mixture was stirred at room temperature for 30 hours
9. 9
   Extraktionextracted with dichloromethane
10. 10
    Trocknendried over sodium sulfate
11. 11
    Einengenconcentrated
12. 12
    SonstigeThe resulting oil was chromatographed on silica gel
13. 13
    Wascheneluting with methanol:ethyl acetate: triethylamine (8.5:1.5:0.3)

Vorschrift

To a solution of 7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine (42 mg) from Example 20 in DMF (1 mL) was added 60% sodium hydride suspension (5 mg), and the mixture was stirred at room temperature for 0.5 hour. To the reaction mixture was added N,N'-Bis(tert-butoxycarbonyl)-N-(ethyl)-S-(ethyl)isothiourea (37 mg), and the mixture was stirred for 18 hours. The reaction mixture was diluted with dichloromethane (50 mL) and washed with water (2×15 mL). The organic layer was dried with sodium sulfate and concentrated. The resulting oil was purified on silica gel, eluting with methanol:ethyl acetate:triethylamine (8.5:1.5:0.3) to afford a mixture of 7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine (40 mg) and [[[6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidin-7-yl]imino[[1,1-dimethylethoxy) carbonyl]amino]methyl]ethylamino]carbamic acid-1,1-dimethylethyl ester. This mixture was dissolved in anhydrous dichloromethane (0.5 mL) containing 2.6-lutidine (8 mg). Trimethylsilyl trifluoromethanesulfonate (6 mg) was added, and the mixture was stirred at room temperature for 30 hours. The mixture was poured into saturated aqueous sodium bicarbonate, extracted with dichloromethane, dried over sodium sulfate, and concentrated. The resulting oil was chromatographed on silica gel, eluting with methanol:ethyl acetate: triethylamine (8.5:1.5:0.3) to afford the title compound (7 mg), ESMS (1/4 MeOH/CH3CN+0.1% AcOH): m/z (relative intensity) 490.5 (MH+, 100), 491.5 (MH+ +1, 27), 492.5 (MH+ +2, 64).

Quelle