Dimethylformamide → Cabergoline

反応式

[CH2:1]([N:4]1[CH:13]2[CH:8]([C:9]3[CH:19]=[CH:18][CH:17]=[C:16]4[C:10]=3[C:11](=[CH:14][NH:15]4)[CH2:12]2)[CH2:7][C@@H:6]([C:20](O)=[O:21])[CH2:5]1)[CH:2]=[CH2:3].Cl.[CH3:24][N:25]([CH3:34])[CH2:26][CH2:27][CH2:28][N:29]=[C:30]=[N:31][CH2:32][CH3:33].C(N(C(C)C)C(C)C)C.CN(C)C=[O:47]>>[CH3:33][CH2:32][NH:31][C:30]([N:29]([C:20]([C@H:6]1[CH2:5][N:4]([CH2:1][CH:2]=[CH2:3])[C@H:13]2[C@@H:8]([C:9]3[C:10]4[C:11]([CH2:12]2)=[CH:14][NH:15][C:16]=4[CH:17]=[CH:18][CH:19]=3)[CH2:7]1)=[O:21])[CH2:28][CH2:27][CH2:26][N:25]([CH3:24])[CH3:34])=[O:47]

参加物

反応物 4

HCID 6228Dimethylformamide

HCID 81531Diisopropylethylamine

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

HCID 68602383HCID 68602383、化合物

生成物 1

HCID 54746Cabergoline

実験手順

17 g of (9R)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylic acid were suspended in 300 ml of dimethylformamide. 20.6 g of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride were added and 18.2 ml of ethyldiisopropylamine were slowly added drop wise in the reactor vessel. The mixture was stirred for 30 hours at room temperature. The solvent was evaporated when the reaction was finished. Further 60 ml of dichloromethane was added and the obtained solution was washed with 2 portions of 40 ml of 2% water solution of ammonia, 2 portions of 40 ml of water and 40 ml of 10% water solution of NaCl. First two alkaline solutions are extracted again with another 30 ml of dichloromethane and evaporated. The obtained crude cabergoline was purified on the RP-18 column with mobile phase of acetonitrile/water. The obtained solution was extracted with dichloromethane at pH=7. Organic phase was evaporated to the oily, foamy or semi-solid material of amorphous cabergoline with 0.2% (w|w) of total impurities.