反応 #3580

反応方程式

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

収率 14.3%

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

収率 14.3%

溶媒

dichloromethane

DMF

dichloromethane

反応条件

後処理

1. 1
   workup.STIRRINGthe mixture was stirred for 18 hours
2. 2
   洗浄washed with water (2×15 mL)
3. 3
   乾燥The organic layer was dried with sodium sulfate
4. 4
   濃縮concentrated
5. 5
   その他The resulting oil was purified on silica gel
6. 6
   洗浄eluting with methanol:ethyl acetate:triethylamine (8.5:1.5:0.3)
7. 7
   その他to afford
8. 8
   workup.STIRRINGthe mixture was stirred at room temperature for 30 hours
9. 9
   抽出extracted with dichloromethane
10. 10
    乾燥dried over sodium sulfate
11. 11
    濃縮concentrated
12. 12
    その他The resulting oil was chromatographed on silica gel
13. 13
    洗浄eluting with methanol:ethyl acetate: triethylamine (8.5:1.5:0.3)

実験手順

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).

出典