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

HRID 1106181

반응식

HRID 1106181 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 m mol) 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid and 175 ml of dichloromethane, 10.2 ml (75 m mol) triethylamine and 9.5 ml (75 m mol) chlorotrimethylsilane are added and the reaction mixture stirred at room temperature for 1 hour. To a solution of 7.86 g (50 m mol) of N-Acetyl-L-proline in 100 ml of dichloromethane at -10° C., 5.5 ml (50 m mol) of N-methylmorpholine and 6.5 ml (50 m mol) of isobutyl chloroformate are added and stirred at -10° C. for 1/2 hour. To this cold mixed anhydride mixture is added the silylated 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid and the resulting mixture is stirred for 3 hrs in an ice bath and overnight at room temperature. Next, 25 ml of isopropanol is added to the reaction mixture and stirred. The reaction mixture is evaporated and the residue is triturated with ice and water. The solid is 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, m.p. 288°-290° dec. From the filtrate an additional 3.94 g of product is obtained.

후처리

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

출처 및 근거

ORD 기록
ord-a32169fd10f041cba76822b2e56e71c9
출처 데이터셋
uspto-grants-1982_01
특허 번호
US04311698

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