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

HRID 1277797

반응식

HRID 1277797 반응식
[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][CH2:32][CH2:31][C@H:27]1[C:28](O)=[O:29])(=[O:25])[CH3:24].CN1CCOCC1.ClC(OCC(C)C)=O>ClCCl.C(O)(C)C.C(N(CC)CC)C>[C:23]([N:26]1[CH2:33][CH2:32][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]

참가 물질

9

반응물 5

HCID 6397ChlorotrimethylsilaneHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 66141N-Acetyl-L-prolineHCID 129189566-(4-Aminophenyl)-1,2-dihydro-2-oxonicotinic acid

생성물 1

HCID 129189646-[4-(N-acetyl-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid수율 52.2%

시약·촉매·용매 3

HCID 3776Isopropanol용매HCID 6344Dichloromethane용매2회HCID 8471Triethylamine용매

실험 절차

To a suspension of 5.75 g (25 mM) 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid and 175 ml of dichloromethane, 10.5 ml (75 mM) triethylamine and 9.5 ml (75 mM) chlorotrimethylsilane were added and stirred at room temperature for 1 hour. To a solution of 7.86 g (50 mM) of N-Acetyl-L-proline in 100 ml of dichloromethane at -10° C., 5.5 ml (50 mM) of N-methylmorpholine and 6.5 ml (50 mM) of isobutyl chloroformate were added and stirred at -10° C. for 1/2 hour. To this cold mixed anhydride mixture was added the silylated 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid and the resulting mixture was stirred for 3 hrs in an ice bath and overnight at room temperature. Next, 25 ml of isopropanol was added to the reaction mixture and stirred. The reaction mixture was evaporated and the residue was triturated with ice and water. The solid was collected by filtration and washed with water, isopropanol and ether to yield 4.82 g of 6-[4-(N-acetyl-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid, mp 288°-290° dec. From the filtrate an additional 3.94 g of product was obtained.

후처리

  1. additionwere added
  2. stirringstirred at -10° C. for 1/2 hour
  3. stirringthe resulting mixture was stirred for 3 hrs in an ice bath and overnight at room temperature
  4. stirringstirred
  5. customThe reaction mixture was evaporated
  6. customthe residue was triturated with ice and water
  7. filtrationThe solid was collected by filtration
  8. washwashed with water, isopropanol and ether

출처 및 근거

ORD 기록
ord-7491cc8d5c81416faee3f90a185068ca
출처 데이터셋
uspto-grants-1981_07
특허 번호
US04278681

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