4'-Fluoroacetophenone → 5-(4-Fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093763ノート

反応式

HRID 1093763 の反応式
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:21][N:20]=[C:19]([C:22]([OH:24])=O)[CH:18]=2)=[CH:13][CH:12]=1.FC1C=CC(C(=O)C)=CC=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:58][CH2:59][C:60]([N:62]1[CH2:67][CH2:66][CH:65]([O:68][C:69]2[CH:70]=[N:71][CH:72]=[C:73]([Cl:75])[CH:74]=2)[CH2:64][CH2:63]1)=[O:61]>CN(C=O)C.O>[Cl:75][C:73]1[CH:74]=[C:69]([O:68][CH:65]2[CH2:64][CH2:63][N:62]([C:60](=[O:61])[CH2:59][NH:58][C:22]([C:19]3[CH:18]=[C:17]([C:14]4[CH:13]=[CH:12][C:11]([F:10])=[CH:16][CH:15]=4)[O:21][N:20]=3)=[O:24])[CH2:67][CH2:66]2)[CH:70]=[N:71][CH:72]=1

参加物

9

反応物 6

HCID 98284'-FluoroacetophenoneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10963925-(4-Fluorophenyl)-1,2-oxazole-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665916722-Amino-1-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-ethanone hydrochloride

生成物 1

HCID 578744345-(4-Fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide収率 17.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

DIPEA (253 mg, 1.96 mmol) was added to a stirred solution of 5-(4-fluoro-phenyl)-isoxazole-3-carboxylic acid (81 mg, 0.39 mmol) (prepared by the method used for the synthesis of Intermediate 25, starting from 4′-fluoroacetophenone) in DMF (2 mL), followed by HOBt (56 mg, 0.41 mmol) and EDCI.HCl (79 mg, 0.41 mmol). After 2 minutes 2-amino-1-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-ethanone hydrochloride (120 mg, 0.39 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added to the reaction mixture and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure. Purification by recrystallisation from 10% ethyl acetate in hexane afforded 32 mg (17.8% Yield) of 5-(4-fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 459, 92.84%. 1H NMR (300 MHz, CDCl3): δ8.2 (s, 2H), 7.86 (m, 1H), 7.76 (m, 2H), 7.14 (m, 3H), 6.9 (s, 1H), 4.7 (m, 1H), 4.3 (m, 2H), 3.7 (m, 3H), 3.5 (m, 1H), 1.9 (m, 4H).

後処理

  1. customprepared by the method
  2. additionwas added to the reaction mixture
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification
  7. customby recrystallisation from 10% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-06be809f76a448458447dc104b4d13f8
出典データセット
uspto-grants-2012_03
特許番号
US08129376B2

反応ノート

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