Potassium Phosphate, Tribasic → 5-(11-fluoro-5,6-dihydropyrimido[4',5':3,4]pyrido[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595724Notes

Reaction equation

HRID 595724 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]1[C:16]([CH:17]=[CH2:18])=[CH:15][N:14]=[C:13]([C:19]3[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])=[CH:21][C:22]4[O:26][C:25]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=5)=[C:24]([C:34]([NH:36][CH3:37])=[O:35])[C:23]=4[CH:38]=3)[N:12]=1)[NH:6]2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(N(C)C)=O.O>[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:11]4[N:12]=[C:13]([C:19]5[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])=[CH:21][C:22]6[O:26][C:25]([C:27]7[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=7)=[C:24]([C:34]([NH:36][CH3:37])=[O:35])[C:23]=6[CH:38]=5)[N:14]=[CH:15][C:16]=4[CH2:17][CH2:18][N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

5

Reactant 2

HCID 62657Potassium Phosphate, TribasicHCID 903334665-(4-(4-fluoro-1H-indol-2-yl)-5-vinylpyrimidin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 903410345-(11-fluoro-5,6-dihydropyrimido[4',5':3,4]pyrido[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 20.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 5-(4-(4-fluoro-1H-indol-2-yl)-5-vinylpyrimidin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (50 mg, 0.08 mmol) in DMAc (1 mL), K3PO4 (100 mg, 0.37 mmol) was added under N2 protection. The reaction mixture was stirred at 90° C. overnight. Then the mixture was diluted with water and extracted with EtOAc. The organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by prep-HPLC to give the product of 5-(11-fluoro-5,6-dihydropyrimido[4′,5′:3,4]pyrido[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (10 mg, yield: 20.0%). 1H-NMR (CDCl3, 400 MHz) δ 8.75 (s, 1H), 8.36 (s, 1H), 8.00˜8.10 (m, 2H), 7.75 (s, 1H), 7.53 (s, 1H), 7.15˜7.25 (m, 4H), 6.84 (t, J=8.8 Hz, 1H), 6.01 (br s, 1H), 4.41 (t, J=6.4 Hz, 2H), 3.50 (s, 3H), 3.34 (t, J=6.4 Hz, 2H), 3.05 (d, J=4.8 Hz, 3H), 2.83 (s, 3H). MS (M+H)+: 614

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-fddc68ba879a420b8fca0b74fa49a3e2
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

Loading…