Acetic Acid → [1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]carbamic acid tert-butyl ester

HRID 651686Notes

Reaction equation

HRID 651686 reaction equation
[C:1]([O:5][C:6](=[O:24])[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[CH:19]=C[C:17](C#N)=[C:16](N)[CH:15]=2)[C:9]1=[O:23])([CH3:4])([CH3:3])[CH3:2].[N:25]1[CH:30]=[N:29][CH:28]=[N:27][CH:26]=1.C(O)(=O)C>C(O)C>[C:1]([O:5][C:6](=[O:24])[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[CH:19]=[C:26]3[C:17]([C:30]([NH2:25])=[N:29][CH:28]=[N:27]3)=[CH:16][CH:15]=2)[C:9]1=[O:23])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 92621,3,5-TriazineHCID 70121975[1(-3-Amino-4-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl]carbamic acid tert-butyl ester

Product 1

HCID 70070961[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]carbamic acid tert-butyl esterYield 520.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

[1-(3-Amino-4-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl]carbamic acid tert-butyl ester (890 mg, 2.69 mmol) and 1,3,5-triazine (650 mmol, 8 mmol) are combined in ethanol (40 mL), and acetic acid (480 mg, 8 mmol) added. The reaction mixture is refluxed under nitrogen overnight, cooled and presorbed directly onto silica. The product is purified by column chromatography on silica with 5-20% methanol/dichloromethane (containing 0.5% of 28% aqueous ammonium hydroxide). The product factions are combined and concentrated, and the residue left under high vacuum overnight. The product is isolated as a pale yellow powder (0.50 g, 14 mmol).

Workup

  1. temperatureThe reaction mixture is refluxed under nitrogen overnight
  2. temperaturecooled
  3. customThe product is purified by column chromatography on silica with 5-20% methanol/dichloromethane (containing 0.5% of 28% aqueous ammonium hydroxide)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-1405660141034610a51e6e199b73e44c
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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