N-methyl-2-pyrrolidone → N-(4-tert-Butyl-2-cyano-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide

HRID 2404824Notes

Reaction equation

[C:1]([C:5]1[C:10]([OH:11])=[CH:9][C:8]([NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)=[O:14])=[C:7](Br)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:27][N:28]1C(=O)CCC1>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:5]1[C:10]([OH:11])=[CH:9][C:8]([NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)=[O:14])=[C:7]([C:27]#[N:28])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 200 °C

Procedure

To a suspension of N-(4-tert-butyl-2-bromo-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide (C-274) (84 mg, 0.2 mmol), Zn(CN)2 (14 mg, 0.12 mmol) in NMP (1 mL) was added Pd(PPh3)4 (16 mg, 0.014 mmol) under nitrogen. The mixture was heated in a microwave oven at 200° C. for 1 h, filtered and purified using preparative HPLC to give N-(4-tert-butyl-2-cyano-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide (476). 1H NMR (400 MHz, DMSO-d6) δ 13.00 (d, J=6.4 Hz, 1H), 12.91 (s, 1H), 10.72 (s, 1H), 8.89 (d, J=6.8 Hz, 1H), 8.34 (d, J=8.2 Hz, 1H), 8.16 (s, 1H), 7.85-7.75 (m, 2H), 7.56-7.54 (m, 1H), 7.44 (s, 1H), 1.35 (s, 9H); HPLC ret. time 3.42 min, 10-100% CH3CN, 5 min gradient; ESI-MS 362.1 m/z (MH+).

Workup

filtrationfiltered
custompurified

Sources & evidence

ORD record: ord-78a079a01ac846a8a974e0a307c3d241
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802700B2

Reaction notes

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