Ammonium Chloride → 4-[4-[(5-Cyano-furan-2-carbonyl)-amino]-3-(4-methyl-piperidin-1-yl)-phenyl]-piperazine-1-carboxylic acid benzyl ester

HRID 646861Notes

Reaction equation

HRID 646861 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-])=O)=[C:19]([N:26]3[CH2:31][CH2:30][CH:29]([CH3:32])[CH2:28][CH2:27]3)[CH:18]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[NH4+:34].[CH3:35][CH2:36][O:37][C:38]([CH3:40])=O.ClCCl.[CH3:44][CH2:45]O.[OH2:47]>[Fe]>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([NH:23][C:35]([C:36]3[O:37][C:38]([C:40]#[N:34])=[CH:44][CH:45]=3)=[O:47])=[C:19]([N:26]3[CH2:31][CH2:30][CH:29]([CH3:32])[CH2:28][CH2:27]3)[CH:18]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 19096565Water ethanolHCID 21226138Dichloromethane ethylacetateHCID 586385074-[3-(4-Methyl-piperidin-1-yl)-4-nitro-phenyl]-piperazine-1-carboxylic acid benzyl ester

Product 1

HCID 115046544-[4-[(5-Cyano-furan-2-carbonyl)-amino]-3-(4-methyl-piperidin-1-yl)-phenyl]-piperazine-1-carboxylic acid benzyl esterYield 73%

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst

Procedure

A procedure similar to Example 9, step (c) was followed using 153 mg (0.349 mmol) of 4-[3-(4-methyl-piperidin-1-yl)-4-nitro-phenyl]-piperazine-1-carboxylic acid benzyl ester (as prepared in the previous step), 97.7 mg (1.75 mmol) of iron powder, 187 mg (3.49 mmol) of ammonium chloride in 10 mL of EtOH-water (2:1) to afford 104 mg (73%) of the corresponding aniline after chromatography on silica with 4-12% EtOAc-dichloromethane. The aniline (100 mg) together with 33.6 mg (0.245 mmol) of 5-cyanofuran-2-carboxylic acid (as prepared in Example 1), 42.7 μL (0.490 mmol) of oxalyl chloride, and 64.1 μL (0.368 mmol) of DIEA afforded, after chromatography on a 20-g silica SPE column with 2% EtOAc-dichloromethane, 118 mg (91%) of the title compound as a light yellow solid: 1H-NMR (CDCl3; 400 MHz): δ 9.59 (br s, H), 8.31 (d, 1H, J=8.9 Hz), 7.33-7.38 (m, 5H), 7.21, 7.24 (AB q, 2H, J=3.7 Hz), 6.79 (d, 1H, J=2.6 Hz), 6.72 (dd, 1H, J=8.9, 2.6 Hz), 5.17 (s, 2H), 3.66-3.69 (m, 4H), 3.12 (br s, 4H), 2.97-3.00 (m, 2H), 2.69-2.75 (m, 2H), 1.83-1.86 (m, 2H), 1.50-1.65 (m, 1H), 1.46-1.52 (m, 2H) and 1.07 (d, 3H, J=6.2 Hz). Mass spectrum (ESI, m/z): Calcd. for C30H33N5O4, 528.3 (M+H), found 528.1.

Sources & evidence

ORD record
ord-4344a4983edf49268980080c39f01370
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

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