Triethylamine → 3-oxo-N-(5-phenylpyrazin-2-yl)spiro[2-benzofuran-1,4'-piperidine]-1'-carboxamide

HRID 480049Notes

Reaction equation

Cl.[NH:2]1[CH2:7][CH2:6][C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[O:8]2)[CH2:4][CH2:3]1.[C:17]1([C:23]2[N:24]=[CH:25][C:26]([NH:29][C:30](=O)[O:31]C3C=CC=CC=3)=[N:27][CH:28]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(CC)CC)C>C(Cl)(Cl)Cl>[O:16]=[C:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]2([CH2:6][CH2:7][N:2]([C:30]([NH:29][C:26]3[CH:25]=[N:24][C:23]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)=[CH:28][N:27]=3)=[O:31])[CH2:3][CH2:4]2)[O:8]1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of spiro[isobenzofuran-1(3H),4′-piperidine]-3-one hydrochloride (6.24 g, 26.6 mmol), phenyl N-(5-phenyl-2-pyrazinyl)carbamate (7.59 g, 26.0 mmol) and triethylamine (18 mL, 180 mmol) in chloroform (200 mL) was stirred at 80° C. for 3 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate (100 mL). After the organic layer was washed with 10% citric acid aqueous solution (100 mL), 1N aqueous sodium hydroxide (100 mL) and then saturated saline solution (100 mL), the organic layer was dried over anhydrous Na2SO4 and then concentrated. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate=1/2) to provide the subject compound as a colorless solid. The solid was washed with diethyl ether (30 mL) to provide the subject compound (8.23 g) as a crude crystal. The crystal was dissolved in hot ethyl acetate (300 mL). After removal of about 100 mL of ethyl acetate by distillation, the white suspension began to occur. At this point the distillation was stopped and the whole was cooled and then kept at room temperature for 14 hours. The colorless prisms formed was collected by filtration, which was washed with heptane (20 mL). The obtained crystal was dried at 50° C. in vacuo for 6 hours to provide the subject compound (Crystal Form A) (5.17 g) as colorless prisms (melting point 210-211° C.).

Workup

washThe reaction mixture was washed with saturated aqueous sodium bicarbonate (100 mL)
washAfter the organic layer was washed with 10% citric acid aqueous solution (100 mL), 1N aqueous sodium hydroxide (100 mL)
dry with materialsaturated saline solution (100 mL), the organic layer was dried over anhydrous Na2SO4
concentrationconcentrated
customThe residue was purified by column chromatography on silica gel (hexane/ethyl acetate=1/2)

Sources & evidence

ORD record: ord-13bbc0f9860d4db2a6a9df0c3b2b3f80
Source dataset: uspto-grants-2003_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06649624B2

Reaction notes

Loading…