Benzaldehyde → HCID 12019600, compound

HRID 990134Notes

Reaction equation

HRID 990134 reaction equation
[CH3:1][O:2][C:3](=[O:36])[C@H:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:35])[C@H:26]([NH2:34])[CH2:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)=[CH:20][CH:19]=1)[NH:5][C:6]([C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:15][CH3:16])=[S:7].[CH:37](=O)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[C:45](OC(=O)C)(=[O:47])[CH3:46]>ClCCl.C(OC)(OC)OC>[CH3:1][O:2][C:3](=[O:36])[C@H:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[C:25](=[O:35])[C@@H:26]([CH2:27][C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)[N:34]([C:45](=[O:47])[CH3:46])[C@@H:37]2[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[CH:20][CH:19]=1)[NH:5][C:6]([C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:15][CH3:16])=[S:7]

Participants

6

Reactant 3

HCID 240BenzaldehydeHCID 7918Acetic AnhydrideHCID 12019599HCID 12019599, compound

Product 1

HCID 12019600HCID 12019600, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 9005Trimethyl orthoformateSolvent

Procedure

To a solution of 4-[[(2R)-2-amino-1-oxo-3-(pyridin-3-yl)propyl]amino]-N-[(2-ethyl-6-methylphenyl)thioxomethyl]-L-phenylalanine methyl ester (0.224 mmol, 113 mg) in dichloromethane (0.75 mL) and trimethyl orthoformate (0.75 mL), was added benzaldehyde (0.25 mmol, 27.5 mg). After the resulting light yellow solution was stirred for 3 days at room temperature, it was heated to 90° C. (oil bath temperature) and excess acetic anhydride (2.0 mmol, 0.21 mL) was introduced via a syringe. The solution was stirred at 110-120° C. (oil bath temperature) for 6 h, then was cooled to room temperature and the solvents were removed in vacuo. The crude residue was purified by RP-HPLC to obtain 95 mg (67%) of 4-[(2S,4R)-3-acetyl-5-oxo-2-phenyl-4-[(pyridin-3-yl)methyl]imidazolidin-1-yl]-N-[(2-ethyl-6-methylphenyl)thioxomethyl]-L-phenylalanine methyl ester as an amorphous colorless solid. HR MS: Obs. mass, 635.2672. Calcd. mass, 635.2692 (M+H). Another isomer was formed in very minor amount by HPLC (<5%) and not attempted to isolate it.

Workup

  1. additionwas introduced via a syringe
  2. stirringThe solution was stirred at 110-120° C. (oil bath temperature) for 6 h
  3. temperaturewas cooled to room temperature
  4. customthe solvents were removed in vacuo
  5. customThe crude residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-e3f311a2d8144a47bc140429c6d65e6f
Source dataset
uspto-grants-2002_10
Patent number
US06458844B2

Reaction notes

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