Triethylamine → 6-[4-(N-Acetyl-DL-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid

HRID 1106182Notes

Reaction equation

[C:1]([N:4]1[CH2:11][CH2:10][CH2:9][CH:5]1[C:6]([OH:8])=O)(=[O:3])[CH3:2].C(N(CC)CC)C.ClC(OCC(C)C)=O.[NH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[NH:35][C:36](=[O:43])[C:37](=[CH:41][CH:42]=2)[C:38]([OH:40])=[O:39])=[CH:30][CH:29]=1>ClCCl.CN(C)C(=O)C>[C:1]([N:4]1[CH2:11][CH2:10][CH2:9][CH:5]1[C:6]([NH:27][C:28]1[CH:29]=[CH:30][C:31]([C:34]2[NH:35][C:36](=[O:43])[C:37](=[CH:41][CH:42]=2)[C:38]([OH:40])=[O:39])=[CH:32][CH:33]=1)=[O:8])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: -10 °C

Procedure

To a solution of 11.8 g (75 m mol) of N-Acetyl-DL-proline and 10.5 ml (75 m mol) of triethylamine in 150 ml dichloromethane at -15° C., is added 9.75 ml (75 m mol) of isobutyl chloroformate. The reaction mixture is stirred at about -10° C. for 30 min. To this reaction mixture is added a cold solution of 11.5 g (50 m mol) of 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid and 7.7 ml (55 m mol) triethylamine in 200 ml of N,N-dimethylacetamide, which is stirred while cooling in an ice bath for 3 hrs, then overnight at room temperature. The reaction mixture is evaporated to dryness, the residue is triturated with water, and the solid collected by filtration. The solid is washed with water and acetonitrile and dried to yield 13.2 g of 6-[4-(N-Acetyl-DL-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid, m.p. 279°-281° dec.

Workup

stirringis stirred
temperaturewhile cooling in an ice bath for 3 hrs
customovernight
customat room temperature
customThe reaction mixture is evaporated to dryness
customthe residue is triturated with water
filtrationthe solid collected by filtration
washThe solid is washed with water and acetonitrile
customdried

Sources & evidence

ORD record: ord-e8d1097d78cb4ff6a60d1ed2fb1c6646
Source dataset: uspto-grants-1982_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04311698

Reaction notes

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