3-(2,6-Dichlorophenyl)-4-formyl-5-isoxazolecarbonyl chloride → 3-(2,6-Dichlorophenyl)-N-(5-{4-[3-(isobutyrylamino)phenyl]-1-piperidinyl}pentyl)-5-methyl-4-isoxazolecarboxamide

HRID 2087227Notes

Reaction equation

HRID 2087227 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:13]([CH:14]=[O:15])=[C:12]([C:16](Cl)=O)[O:11][N:10]=1.[NH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][N:25]1[CH2:30][CH2:29][CH:28]([C:31]2[CH:32]=[C:33]([NH:37][C:38](=[O:43])[CH:39]([CH2:41]C)[CH3:40])[CH:34]=[CH:35][CH:36]=2)[CH2:27][CH2:26]1>C1COCC1>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[C:9]1[C:13]([C:14]([NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][N:25]2[CH2:26][CH2:27][CH:28]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([NH:37][C:38](=[O:43])[CH:39]([CH3:40])[CH3:41])[CH:32]=3)[CH2:29][CH2:30]2)=[O:15])=[C:12]([CH3:16])[O:11][N:10]=1

Participants

4

Reactant 2

HCID 220486823-(2,6-Dichlorophenyl)-4-formyl-5-isoxazolecarbonyl chlorideHCID 22048959N-{3-[1-(5-aminopentyl)-4-piperidinyl]phenyl}-2-ethylpropanamide

Product 1

HCID 220487233-(2,6-Dichlorophenyl)-N-(5-{4-[3-(isobutyrylamino)phenyl]-1-piperidinyl}pentyl)-5-methyl-4-isoxazolecarboxamideYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-(2,6-dichlorophenyl)-4-formyl-5-isoxazolecarbonyl chloride (69.0 mg, 0.250 mmol), N-{3-[1-(5-aminopentyl)-4-piperidinyl]phenyl}-2-ethylpropanamide (44.0 mg, 0.150 mmol), TEA (30.0 mg, 0.300 mmol) in THF (2 mL) was stirred for 12 h at room temperature. The crude product was purified by preparative TLC using CH2Cl2/MeOH/isopropyl amine (19:1:0.2) to give the desired product (52 mg, 67%). 1H NMR (400 MHz, CDCl3) δ 7.52-7.49 (m, 2H), 7.49-7.41 (m, 2H), 7.39-7.31 (m, 2H), 7.29-7.21 (m, 2H), 6.92 (d, 1H, J=7.6 Hz), 3.25-3.11 (m, 5H), 2.81-2.74 (m, 4H), 2.58-2.44 (m, 4H), 2.30-2.19 (m, 2H), 1.93-1.78 (m, 4H), 1.56-1.44 (m, 2H), 1.31-1.28 (m, 2H), 1.24 (d, 6H, J=6.6 Hz); ESMS m/e: 585.2 (M+H)+.

Workup

  1. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-9f0feee160564107a571fc3ab9c7dd1b
Source dataset
uspto-grants-2004_04
Patent number
US06727264B1

Reaction notes

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