Potassium Phosphate, Tribasic → 5-(6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 1776878Notes

Reaction equation

HRID 1776878 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.Cl[C:43]1[CH:44]=[CH:45][C:46]2[O:51][CH2:50][N:49]3[C:52]4[CH:58]=[CH:57][CH:56]=[CH:55][C:53]=4[N:54]=[C:48]3[C:47]=2[CH:59]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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].O>[CH:59]1[C:47]2[C:48]3[N:49]([C:52]4[CH:58]=[CH:57][CH:56]=[CH:55][C:53]=4[N:54]=3)[CH2:50][O:51][C:46]=2[CH:45]=[CH:44][C:43]=1[C:18]1[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][C:10]2[O:9][C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[C:12]([C:13]([NH:15][CH3:16])=[O:14])[C:11]=2[CH:17]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 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 712956192-chloro-6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazine

Product 1

HCID 715095445-(6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 22%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

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 (117 mg, 0.23 mmol) and 2-chloro-6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazine (60 mg, 0.23 mmol) in dioxane:H2O (2 mL:0.5 mL) was added Pd2(dba)3 (21 mg, 0.02 mmol), X-Phos (22 mg, 0.05 mmol) and K3PO4 (184 mg, 0.69 mmol) under N2. The mixture was heated to 100° C. and stirred for about 15 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was washed with H2O, brine, dried over Na2SO4. After being concentrated in vacuo, the resulting resulting residue was purified using prep-HPLC to provide the product of Compound 133 (30 mg, yield: 22%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.59 (d, J=4.4 Hz, 1H), 8.14 (d, J=1.9 Hz, 1H), 8.08˜8.05 (m, 3H), 7.77˜7.72 (m, 2H), 7.69 (s, 1H), 7.63 (dd, J=8.7, 2.0 Hz, 1H), 7.46 (t, J=8.7 Hz, 2H), 7.37˜7.30 (m, 3H), 6.38 (s, 2H), 3.21 (s, 3H), 3.05 (s, 3H), 2.87 (d, J=4.4 Hz, 3H). MS (M+H)+: 597.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. washThe filtrate was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter being concentrated in vacuo
  6. customthe resulting resulting residue
  7. customwas purified

Sources & evidence

ORD record
ord-c842f1995b974bd9a952a87b7e53905f
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

Loading…