Ammonia → HCID 13823170, compound

HRID 649506Notes

Reaction equation

HRID 649506 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:17]3[C:7]([CH2:8][C@@H:9]4[C@@H:14]([C:15]=3[CH:16]=1)[CH2:13][C@H:12]([NH:18][C:19](=[O:25])[N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])[CH2:11][N:10]4[CH3:26])=[C:6](SC)[NH:5]2.[BH4-].[Na+].N>FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:17]3[C:7]([CH2:8][C@@H:9]4[C@@H:14]([C:15]=3[CH:16]=1)[CH2:13][C@H:12]([NH:18][C:19](=[O:25])[N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])[CH2:11][N:10]4[CH3:26])=[CH:6][NH:5]2

Participants

5

Reactant 3

HCID 222AmmoniaHCID 4311764Sodium borohydrideHCID 13823184HCID 13823184, compound

Product 1

HCID 13823170HCID 13823170, compoundYield 56.4%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Under argon, 10.74 g (23 mmol) of 3-(13-bromo-6-methyl-2-methylthio-8α-ergolinyl)-1,1-diethylurea is dissolved in 200 ml of trifluoroacetic acid. At a temperature of -15° C., sodium borohydride tablets are added thereto in 8 portions of 0.5 g each. After a reaction period of 11/2 hours at -15° C., the mixture is poured on 500 ml of ice, the solution is gently rendered alkaline with 25% strength ammonia solution, and extracted with methylene chloride. The organic phases are dried over magnesium sulfate and evaporated. The crude product is dissolved under argon in 100 ml of methanol p.a. and combined with 50 ml of 7N potassium hydroxide solution. The mixture is stirred for 2 hours at room temperature until the reaction is completed; then the mixture is poured on 150 ml of ice to work it up, and extracted with methylene chloride. The organic phases are washed with water and dried over magnesium sulfate. The concentrated crude product is chromatographed on 1.4 kg of silica gel with methylene chloride/methanol in a ratio of 97:3. In this way, 6.0 g is isolated which is crystallized from ethyl acetate/diisopropyl ether to complete the purification process, thus obtaining 5.44 g of 3-(13-bromo-6-methyl-8α-ergolinyl)-1,1-diethylurea (56% yield).

Workup

  1. extractionextracted with methylene chloride
  2. dry with materialThe organic phases are dried over magnesium sulfate
  3. customevaporated
  4. dissolutionThe crude product is dissolved under argon in 100 ml of methanol
  5. additionthen the mixture is poured on 150 ml of ice
  6. extractionextracted with methylene chloride
  7. washThe organic phases are washed with water
  8. dry with materialdried over magnesium sulfate
  9. concentrationThe concentrated crude product
  10. customis chromatographed on 1.4 kg of silica gel with methylene chloride/methanol in a ratio of 97:3
  11. customIn this way, 6.0 g is isolated which
  12. customis crystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-19d8806ff2754c14b7d4b68eb9e45461
Source dataset
uspto-grants-1988_04
Patent number
US04740509

Reaction notes

Loading…