Aniline → 5-Cyano-N-[4-(4-Methylpiperazin-1-Yl)-2-Piperidin-1-Ylphenyl]furan-2-Carboxamide

HRID 646845

反応式

HRID 646845 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[C:10]([N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[CH:9]=2)[CH2:4][CH2:3]1.NC1C=CC=CC=1.[C:30]([C:32]1[O:36][C:35]([C:37](O)=[O:38])=[CH:34][CH:33]=1)#[N:31].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>[Pd].CN(C=O)C>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:37]([C:35]3[O:36][C:32]([C:30]#[N:31])=[CH:33][CH:34]=3)=[O:38])=[C:10]([N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[CH:9]=2)[CH2:4][CH2:3]1

参加物

8

反応物 5

HCID 6115AnilineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 28857041-Methyl-4-(4-nitro-3-(piperidin-1-yl)phenyl)piperazineHCID 108555165-cyanofuran-2-carboxylic Acid

生成物 1

HCID 115028715-Cyano-N-[4-(4-Methylpiperazin-1-Yl)-2-Piperidin-1-Ylphenyl]furan-2-Carboxamide

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 6228Dimethylformamide溶媒

実験手順

The procedure of Example 4, step (c) was followed using 304 mg (1.00 mmol) 1-methyl-4-(4-nitro-3-piperidin-1-yl-phenyl)-piperazine (as prepared in the previous step) and 304 mg of 10% palladium on carbon (50% by weight water) to prepare the intermediate aniline (4-(4-methyl-piperazin-1-yl)-2-piperidin-1-yl-phenylamine) along with 140 mg (1.02 mmol) of 5-cyanofuran-2-carboxylic acid (as prepared in Example 1), 178 μL (2.04 mmol) of oxalyl chloride, 10 μL of anh DMF, and 267 μL (1.53 mmol) of DIEA to perform the amide coupling. The resulting residue was chromatographed on a 20-g silica SPE column with 2-5% EtOH-dichloromethane to afford, after slow concentration from EtOAc-hexane (1:1), 232 mg (59%) of the title compound as a yellow solid: 1H-NMR (CDCl3; 400 MHz): δ 9.53 (br s, 1H), 8.32 (d, 1H, J=8.9 Hz), 7.25 (d, 1H, J=3.7 Hz, partially obscured by CHCl3 peak), 7.21 (d, 1H, J=3.7 Hz), 6.80 (d, 1H, J=2.7 Hz), 6.73 (dd, 1H, J=8.9, 2.7 Hz), 3.20 (m, 4H), 2.85 (m, 4H), 2.59 (m, 4H), 2.36 (s, 3H), 1.80 (m, 4H), and 1.65 (br m, 2H). Mass spectrum (ESI, m/z): Calcd. for C22H27N5O2, 394.2 (M+H), found 394.2.

後処理

  1. customThe resulting residue was chromatographed on a 20-g silica SPE column with 2-5% EtOH-dichloromethane
  2. customto afford
  3. concentrationafter slow concentration from EtOAc-hexane (1:1), 232 mg (59%) of the title compound as a yellow solid

出典と根拠

ORDレコード
ord-2d5c5329a6f44672b97f183fc9f9fdb0
出典データセット
uspto-grants-2010_04
特許番号
US07705042B2

関連ノート

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