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

HRID 1277797

反応式

HRID 1277797 の反応式
[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]

参加物

9

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 3776Isopropanol溶媒HCID 6344Dichloromethane溶媒2 回HCID 8471Triethylamine溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-7491cc8d5c81416faee3f90a185068ca
出典データセット
uspto-grants-1981_07
特許番号
US04278681

関連ノート

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