반응 #3580

반응 방정식

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

수율 14.3%

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

수율 14.3%

용매

dichloromethane

DMF

dichloromethane

반응 조건

후처리

1. 1
   workup.STIRRINGthe mixture was stirred for 18 hours
2. 2
   세척washed with water (2×15 mL)
3. 3
   건조The organic layer was dried with sodium sulfate
4. 4
   농축concentrated
5. 5
   기타The resulting oil was purified on silica gel
6. 6
   세척eluting with methanol:ethyl acetate:triethylamine (8.5:1.5:0.3)
7. 7
   기타to afford
8. 8
   workup.STIRRINGthe mixture was stirred at room temperature for 30 hours
9. 9
   추출extracted with dichloromethane
10. 10
    건조dried over sodium sulfate
11. 11
    농축concentrated
12. 12
    기타The resulting oil was chromatographed on silica gel
13. 13
    세척eluting with methanol:ethyl acetate: triethylamine (8.5:1.5:0.3)

실험 절차

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).

출처