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 1093848노트

반응식

HRID 1093848 반응식
[CH3:1][CH2:2][N:3]([CH:7]([CH3:9])C)[CH:4]([CH3:6])[CH3:5].C1(N2C=C([C:18](O)=[O:19])N=N2)CC1.[CH:21]1(N)[CH2:23][CH2:22]1.C1C=CC2N([OH:34])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:34]=[C:7]1[CH2:9][CH2:1][CH2:2][N:3]1[C:4]1[CH:5]=[CH:22][C:23]([C:18]([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:67])([F:65])[F:66])[CH:59]=3)[CH2:55][CH2:56]2)=[O:19])=[CH:21][CH:6]=1

참가 물질

9

반응물 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 665916551-cyclopropyl-1H-1,2,3-triazole-4-carboxylic acid

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 (190 mg, 1.47 mmol) was added to a stirred solution of 1-cyclopropyl-1H-[1,2,3]triazole-4-carboxylic acid (prepared by the method used for the synthesis of Intermediate 64, starting from cyclopropylamine) (50 mg, 0.32 mmol) in DMF (5 mL) followed by HOBt (48 mg, 0.35 mmol) and EDCI (156 mg, 0.81 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 added and the solid precipitate was filtered. The solid 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. customprepared by the method
  2. additionwas added
  3. stirringthe resulting mixture was stirred at room temperature overnight
  4. filtrationthe solid precipitate was filtered
  5. customThe solid was purified by column chromatography (using 60-120 silica gel and 70% ethyl acetate in hexane as eluent)

출처 및 근거

ORD 기록
ord-126d93653e014be7af5ad4f0d3c05ec2
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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