Dimethylformamide → Cabergoline

HRID 2196374Notes

Reaction equation

HRID 2196374 reaction equation
[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]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68602383HCID 68602383, compound

Product 1

HCID 54746Cabergoline

Procedure

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.

Workup

  1. customThe solvent was evaporated when the reaction
  2. additionFurther 60 ml of dichloromethane was added
  3. washthe 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
  4. extractionFirst two alkaline solutions are extracted again with another 30 ml of dichloromethane
  5. customevaporated

Sources & evidence

ORD record
ord-14e1ef68799b45b18b7a7591191fb501
Source dataset
uspto-grants-2012_12
Patent number
US08338445B2

Reaction notes

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