Chlorotrimethylsilane → 6-[4-(N-acetyl-4-oxo-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid

HRID 1277806Notes

Reaction equation

HRID 1277806 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10](=[O:17])[C:11](=[CH:15][CH:16]=2)[C:12]([OH:14])=[O:13])=[CH:4][CH:3]=1.Cl[Si](C)(C)C.[C:23]([N:26]1[CH2:33][C:32](=[O:34])[CH2:31][C@H:27]1[C:28](O)=[O:29])(=[O:25])[CH3:24].CN1CCOCC1.ClC(OC)=O.O=C1N=CC=CC1C(O)=O>ClCCl.C(N(CC)CC)C>[C:23]([N:26]1[CH2:33][C:32](=[O:34])[CH2:31][C@H:27]1[C:28]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:9][C:10](=[O:17])[C:11](=[CH:15][CH:16]=2)[C:12]([OH:14])=[O:13])=[CH:6][CH:7]=1)=[O:29])(=[O:25])[CH3:24]

Participants

9

Reactant 6

HCID 6397ChlorotrimethylsilaneHCID 6586Methyl chloroformateHCID 79724-MethylmorpholineHCID 129189566-(4-Aminophenyl)-1,2-dihydro-2-oxonicotinic acidHCID 12918986(2S)-1-acetyl-4-oxopyrrolidine-2-carboxylic acidHCID 219955862-Oxo-2,3-dihydropyridine-3-carboxylic acid

Product 1

HCID 705283846-[4-(N-acetyl-4-oxo-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinic acidYield 90.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

A suspension of 8.0 g (34.6 mM) of 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid, 10 g (99 mM of triethylamine, and 560 ml of dichloromethane was stirred at room temperature for 11.3 g (0.104 mol) of chlorotrimethylsilane was added and solution was observed in 30 min. A suspension of 11.9 g (0.069 mol) of N-acetyl-4-oxo-L-proline in 160 ml of dichloromethane was stirred at -10° and 6.9 g (0.069 mol) of N-methylmorpholine was added followed by 6.6 g (0.069 mol) of methyl chloroformate over a ten min period. The reaction was stirred at -10° for 30 min and cooled to -30°. The above oxonicotinic acid solution was added in aliquots keeping the temperature below -5°, and the reaction mixture was stirred in an ice bath overnight, allowing the bath to come to room temperature. The reaction was evaporated to a gum and water was added. The resulting solid was filtered, dried, and digested with hot ethanol. The purified solid was filtered and dried to give 12 g of 6-[4-(N-acetyl-4-oxo-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid;

Workup

  1. additionwas added
  2. stirringThe reaction was stirred at -10° for 30 min
  3. temperaturecooled to -30°
  4. customthe temperature below -5°
  5. stirringthe reaction mixture was stirred in an ice bath overnight
  6. customto come to room temperature
  7. customThe reaction was evaporated to a gum and water
  8. additionwas added
  9. filtrationThe resulting solid was filtered
  10. customdried
  11. filtrationThe purified solid was filtered
  12. customdried

Sources & evidence

ORD record
ord-7f06e31527c64b00813115de88fa5b6f
Source dataset
uspto-grants-1981_07
Patent number
US04278681

Reaction notes

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