Potassium Iodide → HCID 11287642、化合物

HRID 1785956ノート

反応式

HRID 1785956 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([C@H:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]([C:22]([C:24]3[CH:25]=[N:26]N(C(C)C)C=3)=[O:23])[C@@H:14]([CH3:32])[CH2:13]2)[C:9](=[O:11])[CH3:10])=[CH:4][CH:3]=1.C([N:36]1[CH:40]=[C:39]([C:41](Cl)=[O:42])C=N1)(C)C.Br[CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47].[C:51](=[O:54])([O-])[O-:52].[K+].[K+].[I-].[K+].CN([CH:62]=[O:63])C>O>[C:9]([N:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[C@H:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]([C:22]([C:41]2[O:42][N:36]=[C:40]([O:52][CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH:39]=2)=[O:23])[C@@H:14]([CH3:32])[CH2:13]1)(=[O:11])[CH3:10].[CH2:41]([O:42][C:62](=[O:63])[CH2:51][O:54][C:25]1[CH:24]=[C:22]([C:46]([O:48][CH3:49])=[O:47])[O:23][N:26]=1)[CH3:39]

参加物

9

反応物 6

HCID 4875Potassium IodideHCID 6228DimethylformamideHCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 11510715HCID 11510715、化合物HCID 60136483HCID 60136483、化合物

生成物 2

HCID 11287642HCID 11287642、化合物収率 60%HCID 86601698HCID 86601698、化合物

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

Ethyl [(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}isoxazol-3-yl)oxy]acetate was prepared following the procedure for N-(4-chlorophenyl)-N-{(2S,4R)-1-[(1-isopropyl-1H-pyrazol-4-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide substituting ethyl {[5-(chlorocarbonyl)isoxazol-3-yl]oxy}acetate for 1-isopropyl-1H-pyrazole-4-carbonyl chloride. (Ethyl {[15-chlorocarbonyl)isoxazol-3-yl]oxy}acetate was prepared in 4 steps from methyl 3-hydroxy 5-isoxazole carboxylate. Methyl 3-hydroxy 5-isoxazole carboxylate (1.00 g, 6.95 mmol) was alkylated using ethyl bromoacetate (0.850 mL, 7.64 mmol) in presence of potassium carbonate (1.05 g, 7.64 mmol) and catalytic potassium iodide in DMF (3.00 mL) at room temperature overnight. Water was added to the reaction mixture and extracted with ethyl acetate. The organics were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to yield the desired methyl 3-(2-ethoxy-2-oxoethoxy)isoxazole-5-carboxylate (60%). (Ref: WO 03/063800 PCT/US03/03224). Methyl 3-(2-ethoxy-2-oxoethoxy)isoxazole-5-carboxylate was further treated with aqueous 5% sodium hydroxide in methanol to yield 3-(carboxymethoxy)isoxazole-5-carboxylic acid (86%). This diacid (0.700 g, 3.76 mmol) was selectively esterified in the presence of catalytic p-toluenesulfonic acid monohydrate (100 mg) in ethanol at room temperature. Water was added to the reaction and the mixture was extracted with ethyl acetate. The organics were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give the desired 3-(2-ethoxy-2-oxoethoxy)isoxazole-5-carboxylic acid (90%). 3-(2-Ethoxy-2-oxoethoxy)isoxazole-5-carboxylic acid was treated with oxalyl chloride and catalytic DMF in dichloromethane to yield the desired ethyl {[5-(chlorocarbonyl)isoxazol-3-yl]oxy}acetate). Ethyl [(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}isoxazol-3-yl)oxy]acetate was treated with a solution of lithium hydroxide monohydrate (aq) in methanol at room temperature overnight to afford [(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}isoxazol-3-yl)oxy]acetic acid in 60% yield.

後処理

  1. customat room temperature
  2. customovernight
  3. extractionextracted with ethyl acetate
  4. washThe organics were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-2b7043dea18c49ecaa89891f8f1cfd79
出典データセット
uspto-grants-2009_03
特許番号
US07504508B2

反応ノート

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