Oxalyl chloride → 5-Cyano-furan-2-carboxylic acid (5-morpholin-4-yl-2-piperidin-1-yl-phenyl)-amide

HRID 646854Notes

Reaction equation

HRID 646854 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[CH:7]=[CH:8][C:9]=1[N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)([O-])=O.[C:22]([C:24]1[O:28][C:27]([C:29](O)=[O:30])=[CH:26][CH:25]=1)#[N:23].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>[Pd]>[N:16]1([C:6]2[CH:7]=[CH:8][C:9]([N:10]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)=[C:4]([NH:1][C:29]([C:27]3[O:28][C:24]([C:22]#[N:23])=[CH:25][CH:26]=3)=[O:30])[CH:5]=2)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 108555165-cyanofuran-2-carboxylic AcidHCID 586385494-(3-Nitro-4-piperidin-1-yl-phenyl)-morpholine

Product 1

HCID 115017865-Cyano-furan-2-carboxylic acid (5-morpholin-4-yl-2-piperidin-1-yl-phenyl)-amideYield 45.4%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

The title compound was prepared following the procedure of Example 5, step (b) using 76.7 mg (0.318 mmol) of 4-(3-nitro-4-piperidin-1-yl-phenyl)-morpholine (as prepared in the previous step), 50 mg of 10% palladium on carbon (50% by weight water), 43.6 mg (0.318 mmol) of 5-cyanofuran-2-carboxylic acid (as prepared in Example 1), 55.5 μL (0.636 mmol) of oxalyl chloride, and 83.1 μL (0.477 mmol) of DIEA. The resulting residue was chromatographed on a 10-g silica SPE column with 15-25% EtOAc-hexane to afford 54.9 mg (45%) of the title compound as a light yellow solid: 1H-NMR (CDCl3; 400 MHz): δ 9.97 (br s, 1H), 8.17 (d, 1H, J=2.8 Hz), 7.23, 7.26 (AB q, 2H, J=3.7 Hz), 7.13 (d, 1H, J=8.7 Hz), 6.66 (dd, 1H, J=8.7, 2.8 Hz), 3.84-3.87 (m, 4H), 23.17-3.19 (m, 4H), 2.75-2.85 (m, 4H), 1.77-1.82 (m, 4H), and 1.5-1.7 (br m, 2H). Mass spectrum (ESI, m/z): Calcd. for C21H24N4O3, 381.2 (M+H), found 381.2.

Workup

  1. customThe title compound was prepared
  2. customThe resulting residue was chromatographed on a 10-g silica SPE column with 15-25% EtOAc-hexane

Sources & evidence

ORD record
ord-607e91286ce84ad0a7add18eea2e0c70
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

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