Triethylamine → 1-[3-[[[4'-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl][1,1'-biphenyl]-4-yl]carbonyl]amino]propyl]-N,N-diethyl-D-lysergamide

HRID 1016666Notes

Reaction equation

HRID 1016666 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][C:4](=[O:7])[N:3]1[O:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23](Cl)=[O:24])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)=[O:10].[NH2:26][CH2:27][CH2:28][CH2:29][N:30]1[C:51]2[C:52]3[C:32]([CH2:33][C@@H:34]4[C:46]([C:47]=3[CH:48]=[CH:49][CH:50]=2)=[CH:45][C@@H:37]([C:38](=[O:44])[N:39]([CH2:42][CH3:43])[CH2:40][CH3:41])[CH2:36][N:35]4[CH3:53])=[CH:31]1.C(N(CC)CC)C>C1COCC1>[O:1]=[C:2]1[CH2:6][CH2:5][C:4](=[O:7])[N:3]1[O:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([NH:26][CH2:27][CH2:28][CH2:29][N:30]3[C:51]4[C:52]5[C:32]([CH2:33][C@@H:34]6[C:46]([C:47]=5[CH:48]=[CH:49][CH:50]=4)=[CH:45][C@@H:37]([C:38](=[O:44])[N:39]([CH2:40][CH3:41])[CH2:42][CH3:43])[CH2:36][N:35]6[CH3:53])=[CH:31]3)=[O:24])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)=[O:10]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 184075094'-[[(2,5-Dioxo-1-pyrrolidinyl)oxy]carbonyl][1,1'-biphenyl]-4-carbonyl chlorideHCID 228945531-(3-aminopropyl)-N,N-diethyl-D-lysergamide

Product 1

HCID 228945511-[3-[[[4'-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl][1,1'-biphenyl]-4-yl]carbonyl]amino]propyl]-N,N-diethyl-D-lysergamideYield 39.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 850 mg (2.375 mmol) of 12 in 65 mL of dry THF under argon was cooled to 0° C. in an icebath, then treated with a solution of 900 mg (2.365 mmol) of 10 in 50 mL of dry THF and 0.6 mL (4.3 mmol) of triethylamine added dropwise over a 20 minute period. The reaction mixture was stirred at 0° C. for 1 hour, then warmed to room temperature, with stirring, for 1 hour. The mixture was concentrated at reduced pressure and the residue was dissolved in 100 mL of methylene chloride. The solution was washed with 100 mL of H2O, 100 mL of saturated sodium bicarbonate solution, 100 mL of saturated brine solution, dried over anhydrous sodium sulfate and concentrated at reduced pressure to a brown residue. This was chromatographed on a short column of 100 g of silica gel using first methylene chloride as eluent, then 9:1 methylene chloride-ether as eluent to elute front running impurities, then 14:1 methylene chloride-isopropyl alcohol as eluent to elute the product to yield 650 mg (39%) of 13 as a cream colored solid [α]D=+34.3° (c=0.45%; CHCl3).

Workup

  1. additionadded dropwise over a 20 minute period
  2. temperaturewarmed to room temperature
  3. stirringwith stirring, for 1 hour
  4. concentrationThe mixture was concentrated at reduced pressure
  5. dissolutionthe residue was dissolved in 100 mL of methylene chloride
  6. washThe solution was washed with 100 mL of H2O, 100 mL of saturated sodium bicarbonate solution, 100 mL of saturated brine solution
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated at reduced pressure to a brown residue
  9. customThis was chromatographed on a short column of 100 g of silica gel using first methylene chloride as eluent
  10. wash9:1 methylene chloride-ether as eluent to elute front
  11. wash14:1 methylene chloride-isopropyl alcohol as eluent to elute the product

Sources & evidence

ORD record
ord-caade618a41643b485a27e01b242910c
Source dataset
uspto-grants-2002_11
Patent number
US06476199B1

Reaction notes

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