Dimethylformamide → PD 161570

반응식

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:28]([NH2:29])=[N:27][C:12]2[N:13]=[C:14]([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[N:15]=[CH:16][C:11]=2[CH:10]=1.[H-].[Na+].[C:32]1([N:38]=[C:39]=[O:40])[CH:37]=CC=C[CH:33]=1.[CH3:41]N(C=O)C>>[C:32]([NH:38][C:39]([NH:29][C:28]1[C:9]([C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=2[Cl:8])=[CH:10][C:11]2[CH:16]=[N:15][C:14]([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[N:13][C:12]=2[N:27]=1)=[O:40])([CH3:41])([CH3:37])[CH3:33]

참가 물질

반응물 4

HCID 6228Dimethylformamide

HCID 7672Phenyl isocyanate

HCID 24758Sodium hydride

HCID 53281336-(2,6-dichlorophenyl)-2-N-[4-(diethylamino)butyl]pyrido[2,3-d]pyrimidine-2,7-diamine

생성물 1

HCID 5328135PD 161570

실험 절차

To a solution of 6-(2,6-dichlorophenyl)-N2 -(4-diethylamino-butyl)-pyrido[2,3-d]pyrimidine-2,7-diamine (25.0 g) from Example 53 in DMF (300 mL) was added 1 equivalent of 60% sodium hydride suspension (2.31 g). After stirring for approximately 2 hours at room temperature, one equivalent of phenyl isocyanate (5.72 g) was added and the reaction monitored by thin layer chromatography After approximately 24 hours, the solvent was removed in vacuo. The residue was dissolved in dichloromethane and this solution was washed several times, first with water and then a saturated solution of sodium chloride. The dichloromethane layer was dried with magnesium sulfate and concentrated in vacuo. Chromatography of the residue on silica gel eluting with ethyl acetate:ethanol:triethylamine (9:2:1), followed by crystallization from tert-butyl methyl ester gave 21.58 g of the title compound 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-(4-diethylamino-butylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea, ESMS (20/80 MeOH/CH3CN+0.1% AcOH): M+ +H=532; mp dec 157° C.