Oxalyl chloride → 5-Cyano-furan-2-carboxylic acid [5-(4-methyl-piperazin-1-yl)-2-piperidin-1-yl-phenyl]-amide

HRID 646852Notes

Reaction equation

HRID 646852 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)=[C:10]([N+:20]([O-])=O)[CH:9]=2)[CH2:4][CH2:3]1.[C:23]([C:25]1[O:29][C:28]([C:30](O)=[O:31])=[CH:27][CH:26]=1)#[N:24].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>[Pd]>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)=[C:10]([NH:20][C:30]([C:28]3[O:29][C:25]([C:23]#[N:24])=[CH:26][CH:27]=3)=[O:31])[CH:9]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 108555165-cyanofuran-2-carboxylic AcidHCID 586384911-Methyl4-(3-nitro-4-piperidin-1-yl-phenyl)-piperazine

Product 1

HCID 117038755-Cyano-furan-2-carboxylic acid [5-(4-methyl-piperazin-1-yl)-2-piperidin-1-yl-phenyl]-amideYield 71%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

The title compound was prepared following the procedure of Example 4, step (c) using 28.1 mg (0.0923 mmol) of 1-methyl-4-(3-nitro-4-piperidin-1-yl-phenyl)-piperazine (as prepared in the previous step), 28 mg of 10% palladium on carbon (Degussa type E101-NE/W, 50% by weight water), 12.7 mg (0.0923 mmol) of 5-cyanofuran-2-carboxylic acid (as prepared in Example 1), 16.2 μL (0.185 mmol) of oxalyl chloride, and 24.1 μL (0.138 mmol) of DIEA. The resulting residue was chromatographed on a 10-g silica SPE column with 1-4% MeOH-dichloromethane to afford 25.8 mg (71%) of the title compound as a beige crystalline solid: 1H-NMR (CDCl3; 400 MHz): δ 9.97 (br s, 1H), 8.18 (d, 1H, J=2.8 Hz), 7.23, 7.25 (AB q, 2H, J=3.7 Hz), 7.11 (d, 1H, J=8.7 Hz), 6.67 (dd, 1H, J=8.7, 2.8 Hz), 3.22-3.25 (m, 4H), 2.75-2.85 (m, 4H), 2.56-2.58 (m, 4H), 2.35 (s, 3H), 1.76-1.81 (m, 4H), and 1.5-1.7 (br m, 2H). Mass spectrum (ESI, m/z): Calcd. for C22H27N5O2, 394.2 (M+H), found 394.2.

Workup

  1. customThe title compound was prepared
  2. customThe resulting residue was chromatographed on a 10-g silica SPE column with 1-4% MeOH-dichloromethane

Sources & evidence

ORD record
ord-83ae2b33de0645e5a283b11f2dd5a2f4
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

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