Potassium Phosphate, Tribasic → 5-(3-(4-fluorobenzyl)-4-oxo-3,4-dihydro-2H-pyrido[3,2-e][1,3]oxazin-6-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 2201543Notes

Reaction equation

HRID 2201543 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18](C4C=CC=C(B5OC(C)(C)C(C)(C)O5)C=4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.Br[C:43]1[CH:52]=[N:51][C:50]2[O:49][CH2:48][N:47]([CH2:53][C:54]3[CH:59]=[CH:58][C:57]([F:60])=[CH:56][CH:55]=3)[C:46](=[O:61])[C:45]=2[CH:44]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:60][C:57]1[CH:58]=[CH:59][C:54]([CH2:53][N:47]2[C:46](=[O:61])[C:45]3[CH:44]=[C:43]([C:18]4[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][C:10]5[O:9][C:8]([C:5]6[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=6)=[C:12]([C:13]([NH:15][CH3:16])=[O:14])[C:11]=5[CH:17]=4)[CH:52]=[N:51][C:50]=3[O:49][CH2:48]2)=[CH:55][CH:56]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 674032762-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzofuran-3-carboxamideHCID 1178015266-bromo-3-(4-fluorobenzyl)-2H-pyrido[3,2-e][1,3]oxazin-4(3H)-one

Product 1

HCID 870558925-(3-(4-fluorobenzyl)-4-oxo-3,4-dihydro-2H-pyrido[3,2-e][1,3]oxazin-6-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 70.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzofuran-3-carboxamide (98 mg, 0.19 mmol) and 6-bromo-3-(4-fluorobenzyl)-2H-pyrido[3,2-e][1,3]oxazin-4(3H)-one (60 mg, 0.18 mmol) in DMF (2 mL) were added Pd(dppf)Cl2 (16 mg, 0.02 mmol) and K3PO4 (270 mg, 0.54 mmol) under N2. After being stirred at 100° C. overnight, the reaction mixture was cooled to RT and filtered. The filtrate was washed with brine and dried over Na2SO4. After being concentrated, the residue was purified by prep-TLC (PE:EtOAc=1:1) to give the product of 5-(3-(4-fluorobenzyl)-4-oxo-3,4-dihydro-2H-pyrido[3,2-e][1,3]oxazin-6-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (80 mg, yield: 70%). 1H-NMR (CDCl3, 400 MHz) δ 8.48 (d, J=2.4 Hz, 1H), 8.44 (d, J=2.4 Hz, 1H), 7.94 (dd, J=5.2, 8.8 Hz, 2H), 7.86 (s, 1H), 7.65 (s, 1H), 7.35 (dd, J=5.2, 8.4 Hz, 2H), 7.22 (t, J=8.8 Hz, 2H), 7.07 (t, J=8.8 Hz, 2H), 5.86 (d, J=4.4 Hz, 1H), 5.31 (s, 2H), 4.75 (s, 2H), 3.21 (s, 3H), 3.00 (d, J=5.2 Hz, 3H), 2.86 (s, 3H). MS (M+H)+: 633.

Workup

  1. temperaturethe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter being concentrated
  6. customthe residue was purified by prep-TLC (PE:EtOAc=1:1)

Sources & evidence

ORD record
ord-0dbefd8618d14a55a54ad1e2247044da
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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