Trifluoroacetic acid → N-(2-aminobenzyl)-3-isobutyl-1-oxo-3-phenyl-3,4,6,7-tetrahydrofuro[3,4-c]pyridine-5(1H)-carboxamide

HRID 1747731Notes

Reaction equation

[CH2:1]([C:5]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:9]2[CH2:10][N:11]([C:14]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[NH:24]C(=O)OC(C)(C)C)=[O:15])[CH2:12][CH2:13][C:8]=2[C:7](=[O:32])[O:6]1)[CH:2]([CH3:4])[CH3:3].C(O)(C(F)(F)F)=O>ClCCl>[NH2:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH2:17][NH:16][C:14]([N:11]1[CH2:12][CH2:13][C:8]2[C:7](=[O:32])[O:6][C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:9]=2[CH2:10]1)=[O:15]

Participants

Conditions

Temperature: 0 °C

Procedure

To an ice-cold solution of tert-butyl 2-((3-isobutyl-1-oxo-3-phenyl-1,3,4,5,6,7-hexahydrofuro[3,4-c]pyridine-5-carboxamido)methyl)phenylcarbamate (62 mg, 0.119 mmol) in dichloromethane (5 mL) was added TFA (1 mL). The reaction mixture stirred at 0° C. for 5 hours and concentrated to dryness to provide crude N-(2-aminobenzyl)-3-isobutyl-1-oxo-3-phenyl-3,4,6,7-tetrahydrofuro[3,4-c]pyridine-5(1H)-carboxamide. The residue was added to a solution of 2-phenylacetic acid (32 mg, 0.238 mmol), BOP (79 mg, 0.179 mmol), and N,N′-diisopropylethylamine (62 mg, 0.477 mmol) in dichloromethane (5 mL), and stirred at room temperature for 16 hours. The crude reaction mixture was concentrated to dryness and purified by column chromatography (12 g, SiO2, 0 to 100% ethyl acetate in hexanes) to provide 3-isobutyl-1-oxo-3-phenyl-N-(2-(2-phenylacetamido)benzyl)-3,4,6,7-tetrahydrofuro[3,4-c]pyridine-5(1H)-carboxamide (66 mg, 93%) as a colorless oil: 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.81-0.98 (m, 6H), 1.65 (dd, J=11.87, 6.59 Hz, 1H), 1.73-1.84 (m, 1H), 2.24-2.47 (m, 4H), 3.30 (dt, J=13.19, 6.22 Hz, 1H), 3.52 (dt, J=13.56, 5.09 Hz, 1H), 3.75 (s, 2H), 3.91 (d, J=18.84 Hz, 1H), 4.21-4.48 (m, 2H), 5.22 (br. s., 1H), 6.97-7.09 (m, 1H), 6.99-7.10 (m, 1H), 7.18 (d, J=6.78 Hz, 1H), 7.23-7.47 (m, 9H), 7.75 (br. s., 1H), 7.96 (d, J=7.91 Hz, 1H), 9.65 (br. s., 1H); MS m/z 538 (M+H)+, 560 (M+23)+, 536 (M−H)−.

Workup

concentrationconcentrated to dryness

Sources & evidence

ORD record: ord-4c2410902ca74feca16417a48d32567c
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09150582B2

Reaction notes

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