3-Bromo-3'-(trifluoromethyl)benzanilide → 3-[2-(methylthio)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-N-[3-(trifluoromethyl)phenyl]benzamide

HRID 1052056Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=1)=[O:6].[CH3:21][S:22][C:23]1[N:24]=[CH:25][C:26]2[CH2:32][NH:31][CH2:30][CH2:29][C:27]=2[N:28]=1.CC(C)([O-])C.[Na+]>C1COCC1.CCOC(C)=O.CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C>[CH3:21][S:22][C:23]1[N:24]=[CH:25][C:26]2[CH2:32][N:31]([C:2]3[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=3)[C:5]([NH:7][C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=3)=[O:6])[CH2:30][CH2:29][C:27]=2[N:28]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 3-bromo-N-[3-(trifluoromethyl)phenyl]benzamide (379 mg, 1.10 mmol), 2-(methylsulfanyl)-5,6,7,8-tetrahydropyrido[4,3-d]-pyrimidine (200 mg, 1.10 mmol), RuPhos (15.4 mg, 0.033 mmol), Cl-RuPhos-Pd precatalyst (24 mg, 0.033 mmol), and sodium-t-butoxide (148 mg, 1.54 mmol) in anhydrous THF (30 ml) was heated at 80° C. under nitrogen for 21 hours. Upon cooling, the reaction mixture was diluted with EtOAc and the insolubles were filtered off (celite). The filtrate was concentrated and the residue was eluted through a flash column (silica gel 60, 230-400 mesh, 1:1 hexanes:EtOAc) to obtain a yellow, crystalline solid (389 mg, 80%).

Workup

temperatureUpon cooling
filtrationthe insolubles were filtered off (celite)
concentrationThe filtrate was concentrated
washthe residue was eluted through a flash column (silica gel 60, 230-400 mesh, 1:1 hexanes:EtOAc)

Sources & evidence

ORD record: ord-3539734433024f47b9bba497728f553b
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09388176B2

Reaction notes

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