1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093856노트

반응식

HRID 1093856 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]=[CH: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.Cl.[NH2:46][CH2:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53]([O:56][C:57]2[CH:62]=[C:61]([F:63])[CH:60]=[CH:59][C:58]=2[F:64])[CH2:52][CH2:51]1)=[O:49]>CN(C=O)C.O>[F:64][C:58]1[CH:59]=[CH:60][C:61]([F:63])=[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]=[CH: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 234450471-Phenyl-1H-imidazole-4-carboxylic acidHCID 665927652-Amino-1-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

생성물 1

HCID 442350231-phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide수율 49.6%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

DIPEA (170 mg, 1.3 mmol) was added to a stirred solution of 1-phenyl-1H-imidazole-4-carboxylic acid (55 mg, 0.29 mmol) in DMF (5 mL) followed by HOBt (43 mg, 0.32 mmol) and EDCI (140 mg, 0.7 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (98.5 mg, 0.32 mmol) was added and the resulting mixture was stirred 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. The residue obtained was purified by washing with ether to afford 63.5 mg (49.6% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 441.17. 1H NMR (300 MHz, DMSO-d6): δ 8.4 (s, 1H), 8.3 (s, 1H), 8.08 (t, 1H), 7.8 (d, 2H), 7.6 (t, 2H), 7.44 (t, 1H), 7.3 (m, 1H), 6.84 (m, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 4.0 (bs, 1H), 3.8 (bs, 1H), 3.7 (bs, 2H), 3.5 (bs, 1H), 2.1 (t, 2H), 1.8 (d, 2H).

후처리

  1. additionwas added
  2. stirringthe resulting mixture was stirred at ambient temperature overnight
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue obtained
  7. customwas purified
  8. washby washing with ether

출처 및 근거

ORD 기록
ord-5b8e3a07322840f59ac2b1b300422a43
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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