1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ningetinib

HRID 2277372Notes

Reaction equation

[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH2:18][C:19]([CH3:22])([OH:21])[CH3:20])=[CH:14][CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[C:4]([F:25])[CH:3]=1.[CH3:26][N:27]1[C:31]([CH3:32])=[C:30]([C:33](O)=[O:34])[C:29](=[O:36])[N:28]1[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>ClCCl.C(OCC)(=O)C>[F:25][C:4]1[CH:3]=[C:2]([NH:1][C:33]([C:30]2[C:29](=[O:36])[N:28]([C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[N:27]([CH3:26])[C:31]=2[CH3:32])=[O:34])[CH:24]=[CH:23][C:5]=1[O:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][C:19]([OH:21])([CH3:22])[CH3:20])=[CH:14][CH:15]=2)[N:10]=[CH:9][CH:8]=1

Participants

Conditions

Temperature: 41 °C

Procedure

To a solution of 1-((4-(4-amino-2-fluorophenoxy)quinolin-7-yl)oxy)-2-methylpropan-2-ol (5 g, 14.6 mmol), 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (3.46 g, 14.9 mmol) and HOAT (0.39 g, 2.9 mmol) in dichloromethane (30 mL) was added EDCI (3.35 g, 17.5 mmol). The mixture was stirred at 41° C. for 6 hours, cooled to room temperature and diluted with ethyl acetate (30 mL). The resulted suspension was filtered, and the solid was washed with 95% ethanol (50 mL×2). The solid was collected through filtration and dried in vacuo at 45° C. for 6 hours to give the title compound as a white solid (6.35 g, 78%).

Workup

temperaturecooled to room temperature
filtrationThe resulted suspension was filtered
washthe solid was washed with 95% ethanol (50 mL×2)
filtrationThe solid was collected through filtration
customdried in vacuo at 45° C. for 6 hours

Sources & evidence

ORD record: ord-ba12f8e41e7643ab8fd9a730e1154a4d
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133162B2

Reaction notes

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