Cesium carbonate → N-(6-{[(1R)-2-methyl-1-(trifluoromethyl)propyl]amino}-1-oxo-1,2-dihydrobenzo[c]-1,6-naphthyridin-9-yl)-2-morpholin-4-ylacetamide

HRID 2192993Notes

Reaction equation

Br[C:2]1[CH:25]=[CH:24][C:5]2[C:6]([NH:15][C@@H:16]([C:20]([F:23])([F:22])[F:21])[CH:17]([CH3:19])[CH3:18])=[N:7][C:8]3[CH:9]=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[N:32]1([CH2:38][C:39]([NH2:41])=[O:40])[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:18][CH:17]([CH3:19])[C@@H:16]([NH:15][C:6]1[C:5]2[CH:24]=[CH:25][C:2]([NH:41][C:39](=[O:40])[CH2:38][N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[CH:3][C:4]=2[C:13]2[C:12](=[O:14])[NH:11][CH:10]=[CH:9][C:8]=2[N:7]=1)[C:20]([F:22])([F:21])[F:23]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 9-bromo-6-{[(1R)-2-methyl-1-(trifluoromethyl)propyl]amino}benzo[c]-1,6-naphthyridin-1(2H)-one (30 mg, 0.07 mmol) in dioxane (1 mL) were added cesium carbonate (83 mg, 0.25 mmol), 2-morpholin-4-ylacetamide (10 mg, 0.07 mmol), Xantphos, (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine), (8.3 mg, 0.01 mmol), and Pd2(dba)3 (6.63 mg, 7.24 μmol). The solution was degassed by bubbling nitrogen gas for 5 min and heated to 100° C. for 2 hr. The solution was filtered and purified using reverse phase chromatography 100% H2O to 100% MeCN. LRMS (ESI) calc'd for (C23H27F3N5O3) [M+H]+, 478.2; found 478.1.

Workup

customThe solution was degassed
customby bubbling nitrogen gas for 5 min
filtrationThe solution was filtered
custompurified

Sources & evidence

ORD record: ord-fee94807061a4aa5b4b25dc6c83d96be
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329722B2

Reaction notes

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