Water → (S,S)-N-(2-hydroxycyclopentyl)-1-isopropyl-6-methylergoline-8-carboxamide

HRID 847407Notes

Reaction equation

HRID 847407 reaction equation
[CH:1]([N:4]1[C:18]2[C:19]3[C:6]([CH2:7][C@@H:8]4[C@@H:13]([C:14]=3[CH:15]=[CH:16][CH:17]=2)[CH2:12][CH:11]([C:20]([OH:22])=O)[CH2:10][N:9]4[CH3:23])=[CH:5]1)([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:36][C@@H:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[OH:42].O>CN(C)C=O>[OH:42][CH:38]1[CH2:39][CH2:40][CH2:41][CH:37]1[NH:36][C:20]([C@H:11]1[CH2:12][C@H:13]2[C@H:8]([CH2:7][C:6]3[C:19]4[C:18](=[CH:17][CH:16]=[CH:15][C:14]2=4)[N:4]([CH:1]([CH3:3])[CH3:2])[CH:5]=3)[N:9]([CH3:23])[CH2:10]1)=[O:22]

Participants

6

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 10464306rac-(1R,2R)-2-aminocyclopentan-1-olHCID 570315491-(1-Methylethyl)-6-methylergoline-8-carboxylic acid

Product 1

HCID 67750439(S,S)-N-(2-hydroxycyclopentyl)-1-isopropyl-6-methylergoline-8-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of 6.24 g of 1-isopropyl-6-methylergoline-8-carboxylic acid in 120 ml of dimethylformamide under a nitrogen atmosphere were added 3.2 g of 1,1'-carbonyldiimidazole. After stirring for approximately four hours, a solution of 2.02 g of trans-2-aminocyclopentanol in 40 ml of dimethylformamide was added with stirring. After stirring at room temperature overnight, the mixture was added to water. The resulting precipitate was extracted three times into methylene chloride. The combined organic extracts were washed with a saturated sodium chloride solution, dried over sodium sulfate, and concentrated in vacuo. The resulting solid was purified by preparative high pressure liquid chromatography over silica gel eluting with methylene chloride/methanol/ammonium hydroxide (100:10:1). The appropriate fractions containing the more mobile diastereomer were combined, concentrated to dryness, and crystallized from methanol to provide 1.15 g of the desired title isomer, m.p. 260-263° C. NMR, MS.

Workup

  1. stirringwith stirring
  2. stirringAfter stirring at room temperature overnight
  3. extractionThe resulting precipitate was extracted three times into methylene chloride
  4. washThe combined organic extracts were washed with a saturated sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resulting solid was purified by preparative high pressure liquid chromatography over silica gel eluting with methylene chloride/methanol/ammonium hydroxide (100:10:1)
  8. additionThe appropriate fractions containing the more mobile diastereomer
  9. concentrationconcentrated to dryness
  10. customcrystallized from methanol
  11. customto provide 1.15 g of the desired title isomer, m.p. 260-263° C

Sources & evidence

ORD record
ord-2616661ed5fe448a9e0875047d31469a
Source dataset
uspto-grants-1992_08
Patent number
US05141944

Reaction notes

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