Lithium Chloride → 6-{[(1R)-2-methyl-1-(trifluoromethyl)propyl]amino}-9-(1H-pyrazol-5-yl)benzo[c]-1,6-naphthyridin-1(2H)-one

HRID 2192977Notes

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.[Cl-].[Li+].[NH:28]1[C:32](B(O)O)=[CH:31][CH:30]=[N:29]1>CN(C=O)C.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:19][CH:17]([CH3:18])[C@@H:16]([NH:15][C:6]1[C:5]2[CH:24]=[CH:25][C:2]([C:30]3[NH:29][N:28]=[CH:32][CH:31]=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:23])([F:22])[F:21]

Participants

Conditions

Temperature: 130 °C

Procedure

To a solution of 9-bromo-6-{[(1R)-2-methyl-1-(trifluoromethyl)propyl]amino}benzo[c]-1,6-naphthyridin-1(2H)-one (33 mg, 0.08 mmol) in DMF (1 mL) and sodium carbonate (0.5 mL, 2.0 M), were added lithium chloride (19.7 mg, 0.464 mg), 1H-pyrazol-5-ylboronic acid (17 mg, 0.16 mmol), and palladium tetrakis triphenylphosphine (27 mg). The mixture was degassed with nitrogen and heated in the microwave at 130° C. for 1 hr. The resulting black solution was filtered and purified by reverse phase HPLC to afford 6-{[(1R)-2-methyl-1-(trifluoromethyl)propyl]amino}-9-(1H-pyrazol-5-yl)benzo[c]-1,6-naphthyridin-1(2H)-one. 1H NMR (600 MHz, CD3OD) δ 10.3 (s, 1H), 8.53 (d, 1H), 8.16 (d, 1H), 7.77 (s, 1H), 7.50 (d, 1H), 6.95 (s, 1H), 6.74 (d, 1H), 5.34 (m, 1H), 2.43 (m, 1H), 1.19 (d, 3H), 1.11 (d, 3H). LRMS (ESI) calc'd for (C20H19F3N5O) [M+H]+, 402.2; found 402.1.

Workup

customThe mixture was degassed with nitrogen
filtrationThe resulting black solution was filtered
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-b72163db323745a594cc515844e17cd4
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329722B2

Reaction notes

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