3-Pyrroline → HCID 69883506, compound

HRID 2122058Notes

Reaction equation

HRID 2122058 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:13][C@@H:14]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C@@H:15]([OH:19])[C:16]([OH:18])=O)=[O:12])=[CH:5]2.[NH:27]1[CH2:31][CH:30]=[CH:29][CH2:28]1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>O1CCCC1.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:13][C@@H:14]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C@@H:15]([OH:19])[C:16]([N:27]1[CH2:31][CH:30]=[CH:29][CH2:28]1)=[O:18])=[O:12])=[CH:5]2

Participants

9

Reactant 5

HCID 660593-PyrrolineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 9820849HCID 9820849, compound

Product 1

HCID 69883506HCID 69883506, compoundYield 92.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A 5.00 g (0.0134 mmol) sample of (αR,βS)-β-[[(5-chloro-1H-indol-2-yl)carbonyl]amino]-α-hydroxy-benzenebutanoic acid (Ia) (prepared according to the methods disclosed in the aforementioned U.S. Pat. Nos. 6,107,329, 6,277,877, and 6,297,269) and 3-pyrroline (1.11 g, 0.015 mmol) (Aldrich Chemical Co., Milwaukee, Wis.) were slurried in 100 ml of tetrahydrofuran at a temperature of between 20° and 25° C. The mixture was treated with 0.6 g (0.33 equiv.) of 1-hydroxybenzotriazole hydrate (HOBT) and the mixture was cooled to between 0° and 5° C. N,N-diisopropylethylamine (2.08 ml, 2.1 equiv.) was added to the mixture over 15 minutes at 0° to 5° C. The mixture was then treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (2.78 g, 1.1 equiv.) at −10° to −6° C. The reaction was allowed to warm to about 20° C. and was stirred at ambient temperature for about 24 hours. The reaction mixture was treated with water (50 ml) and ethyl acetate (50 ml) to give a two-phase mixture. The layers were settled and the organic layer was separated and concentrated to furnish a solid by distillation under partial vacuum. A total of 5.1 g (92.7% yield) of the pure title product was isolated.

Workup

  1. temperaturethe mixture was cooled to between 0° and 5° C
  2. customto give a two-phase mixture
  3. customthe organic layer was separated
  4. concentrationconcentrated
  5. customto furnish a solid
  6. distillationby distillation under partial vacuum

Sources & evidence

ORD record
ord-e8d6f469312c4c848c210b0b05e536da
Source dataset
uspto-grants-2004_02
Patent number
US06696574B2

Reaction notes

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