1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-phenyl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093782노트

반응식

HRID 1093782 반응식
CCN(C(C)C)C(C)C.[C:10]1([N:16]2[CH:20]=[C:19]([C:21]([OH:23])=O)[N:18]=[N:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[ClH:45].[NH2:46][CH2:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53]([O:56][C:57]2[CH:62]=[CH:61][CH:60]=[C:59](C(F)(F)F)[CH:58]=2)[CH2:52][CH2:51]1)=[O:49]>CN(C=O)C.O>[Cl:45][C:58]1[CH:59]=[CH:60][CH:61]=[CH:62][C:57]=1[O:56][CH:53]1[CH2:54][CH2:55][N:50]([C:48](=[O:49])[CH2:47][NH:46][C:21]([C:19]2[N:18]=[N:17][N:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:20]=2)=[O:23])[CH2:51][CH2:52]1

참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5551941-Phenyl-1H-1,2,3-triazole-4-carboxylic acidHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

생성물 1

HCID 578743841-phenyl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide수율 50%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

DIPEA (137 mg, 11.0 mmol) was added to stirred solution of 1-phenyl-1H-[1,2,3]triazole-4-carboxylic acid (50 mg, 0.26 mmol) in DMF (3 mL) followed by HOBT (39 mg, 0.29 mmol) and EDCI (100 mg, 0.53 mmol). After 2 minutes of stirring, 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (90 mg, 0.26 mmol) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with cold water and extracted with ethyl acetate. The organic layer collected was dried over sodium sulfate and concentrated under reduced pressure afforded residue. The residue was purified by column chromatography (using 60-120 silica gel and 50% EtOAc in hexane as eluent) afforded 63 mg (50% Yield) of 1-phenyl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 474.14, 94.1%. 1H NMR (300 MHz, DMSO-d6): δ 9.38 (s, 1H), 8.5 (t, 1H), 8.0 (d, 2H), 7.7-7.6 (t, 2H), 7.6-7.5 (t, 2H), 7.36-7.24 (t, 3H), 4.8 (q, 1H), 4.25 (d, 2H), 4.0-3.8 (m, 1H), 3.8-3.7 (m, 1H), 3.5 (m, 2H), 2.0 (m, 2H), 1.8-1.5 (m, 2H).

후처리

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. extractionextracted with ethyl acetate
  4. customThe organic layer collected
  5. dry with materialwas dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customafforded residue
  8. customThe residue was purified by column chromatography (using 60-120 silica gel and 50% EtOAc in hexane as eluent)

출처 및 근거

ORD 기록
ord-d6f56e9a08b142d5b9311ee3befd7c66
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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