2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(2-Fluoro-4-(6-oxo-5,6-dihydrobenzo[c][1,8]naphthyridin-1-ylamino)phenyl) benzamide

HRID 1029250Notes

Reaction equation

Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[C:4]1[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=1[C:6](=[O:12])[NH:7]2.[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24]C2C=CC(NC(=O)C3C=CC=CC=3)=CC=2)=[C:20]([F:40])[CH:19]=1.CC(C1C=C(C(C)C)[C:47]([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC([O-:79])(C)C.[Na+]>O1CCOCC1.CCOC(C)=O.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:40][C:20]1[CH:19]=[C:18]([NH:17][C:2]2[CH:11]=[CH:10][N:9]=[C:8]3[C:3]=2[C:4]2[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=2[C:6](=[O:12])[NH:7]3)[CH:23]=[CH:22][C:21]=1[NH:24][C:47](=[O:79])[C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1

Participants

Conditions

Temperature: 100 °C

Procedure

The reaction mixture of 83 (80 mg, 0.35 mmol), N-(4-(4-amino-2-fluorophenyl amino)phenyl)benzamide (96 mg, 0.42 mmol), Pd(OAc)2 (12 mg, 0.05 mmol), X-Phos (50 mg, 0.10 mmol), and NaOtBu (67 mg, 0.69 mmol) in dioxane (2 mL) was stirred at 100° C. for 2 days. The reaction mixture was diluted with EtOAc/H2O. The resulting precipitate was filtered, washed with H2O, and dried under vacuum to provide 320 (23 mg, 16% yield) as a solid. LC-MS (M+H=425, obsd.=425).

Workup

filtrationThe resulting precipitate was filtered
washwashed with H2O
customdried under vacuum

Sources & evidence

ORD record: ord-bc395ab7e77a4445915329c845280c9b
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08735584B2

Reaction notes

Loading…