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 1093848ノート

反応式

HRID 1093848 の反応式
[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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-126d93653e014be7af5ad4f0d3c05ec2
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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