1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(2-oxo-pyrrolidin-1-yl)-N-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-benzamide

HRID 1093847노트

반응식

HRID 1093847 반응식
CCN(C(C)C)C(C)C.[O:10]=[C:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16]1[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][CH:17]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:47][CH2:48][C:49]([N:51]1[CH2:56][CH2:55][CH:54]([O:57][C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([C:64]([F:67])([F:66])[F:65])[CH:59]=2)[CH2:53][CH2:52]1)=[O:50]>CN(C=O)C.O>[O:10]=[C:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16]1[CH:17]=[CH:18][C:19]([C:20]([NH:47][CH2:48][C:49](=[O:50])[N:51]2[CH2:52][CH2:53][CH:54]([O:57][C:58]3[CH:63]=[CH:62][CH:61]=[C:60]([C:64]([F:65])([F:66])[F:67])[CH:59]=3)[CH2:55][CH2:56]2)=[O:22])=[CH:23][CH:24]=1

참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7731304-(2-Oxopyrrolidin-1-yl)benzoic acidHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

생성물 1

HCID 578744584-(2-oxo-pyrrolidin-1-yl)-N-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-benzamide수율 56.62%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

DIPEA (200 mg, 1.55 mmol) was added to a stirred solution of 4-(2-oxo-pyrrolidin-1-yl)-benzoic acid (70 mg, 0.34 mmol) in DMF (5 mL) followed by HOBt (50 mg, 0.37 mmol) and EDCI (163 mg, 0.85 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) (127 mg, 0.37 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the precipitate was filtered off. The solid obtained was purified by column chromatography (using 60-120 silica gel and 70% ethyl acetate in hexane as eluent) to afford 94 mg (56.62% Yield) of 4-(2-oxo-pyrrolidin-1-yl)-N-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-benzamide. LC/MS [M+H]+: 490.19, 98.95%. 1H NMR (300 MHz, DMSO-d6): δ 8.6 (t, 1H), 7.94 (d, 2H), 7.8 (d, 2H), 7.6 (t, 1H), 7.38 (t, 3H), 4.8 (m, 1H), 4.2 (d, 1H), 4.0 (t, 3H), 3.8 (d, 1H), 3.5 (d, 1H), 3.3 (bs, 1H), 2.5 (bs, 2H), 2.1 (m, 2H), 2.0 (d, 2H), 1.7 (d, 2H).

후처리

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. filtrationthe precipitate was filtered off
  4. customThe solid obtained
  5. customwas purified by column chromatography (using 60-120 silica gel and 70% ethyl acetate in hexane as eluent)

출처 및 근거

ORD 기록
ord-002e95171c744cc99a25dcaa2b75d3e9
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

반응 노트

불러오는 중…