Phenyl isocyanate → HCID 71584708, compound

HRID 1430536Notes

Reaction equation

[NH2:1][C:2]1[C:9]([F:10])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:11]2[C:12](=[O:25])[N:13]([CH2:23][CH3:24])[C:14]3[C:19]([CH:20]=2)=[CH:18][N:17]=[C:16]([NH:21][CH3:22])[CH:15]=3)[CH:3]=1.[Li]CCCC.[C:31]1([N:37]=[C:38]=[O:39])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[C:6]([C:5]1[C:4]([C:11]2[C:12](=[O:25])[N:13]([CH2:23][CH3:24])[C:14]3[C:19]([CH:20]=2)=[CH:18][N:17]=[C:16]([NH:21][CH3:22])[CH:15]=3)=[CH:3][C:2]([NH:1][C:38]([NH:37][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:39])=[C:9]([F:10])[CH:8]=1)#[N:7]

Participants

Conditions

Temperature: -60 °C

Procedure

A −70° C. solution of 4-amino-2-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-5-fluorobenzonitrile (100 mg, 0.296 mmol) in DCM was treated drop-wise with n-BuLi (0.47 mL, 1.17 mmol), stirred at −60° C. for 40 min, treated with phenyl isocyanate (70.6 mg, 0.593 mmol), warmed to RT and stirred for 12 h. The mixture was concentrated and purified by HPLC to afford 1-(4-cyano-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea (22 mg, 16% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.28 (s, 1H), 9.08 (s, 1H), 8.46 (s, 1H), 8.42 (d, J=8.0 Hz, 1H), 7.94 (s, 1H), 7.91 (s, 1H), 7.45-7.43 (m, 2H), 7.31-7.27 (m, 2H), 7.18-7.13 (q, J=4.8 Hz, 1H), 7.02-6.98 (m, 1H), 6.26 (s, 1H), 4.16 (q, J=7.2 Hz, 2H), 2.87 (d, J=4.8 Hz, 3H), 1.22 (t, J=7.2 Hz, 3H); MS (ESI) m/z: 457.3 [M+H]+.

Workup

temperaturewarmed to RT
stirringstirred for 12 h
concentrationThe mixture was concentrated
custompurified by HPLC

Sources & evidence

ORD record: ord-738b0f9595cf41ea8167c167e6190191
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940756B2

Reaction notes

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