Reacción #3580

Ecuación de reacción

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

Rendimiento 14.3%

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

Rendimiento 14.3%

Disolventes

dichloromethane

DMF

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe mixture was stirred for 18 hours
2. 2
   Lavadowashed with water (2×15 mL)
3. 3
   SecadoThe organic layer was dried with sodium sulfate
4. 4
   Concentraciónconcentrated
5. 5
   OtroThe resulting oil was purified on silica gel
6. 6
   Lavadoeluting with methanol:ethyl acetate:triethylamine (8.5:1.5:0.3)
7. 7
   Otroto afford
8. 8
   workup.STIRRINGthe mixture was stirred at room temperature for 30 hours
9. 9
   Extracciónextracted with dichloromethane
10. 10
    Secadodried over sodium sulfate
11. 11
    Concentraciónconcentrated
12. 12
    OtroThe resulting oil was chromatographed on silica gel
13. 13
    Lavadoeluting with methanol:ethyl acetate: triethylamine (8.5:1.5:0.3)

Procedimiento

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).

Fuente