2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide → HCID 87055970, compound

HRID 2201551Notes

Reaction equation

HRID 2201551 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](B4OC(C)(C)C(C)(C)O4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.Br[C:37]1[CH:52]=[N:51][C:40]2[NH:41][CH:42]([C:46]3[S:47][CH:48]=[CH:49][CH:50]=3)[NH:43][C:44](=[O:45])[C:39]=2[CH:38]=1>O1CCOCC1.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:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:23])=[O:24])[C:18]([C:37]4[CH:52]=[N:51][C:40]5[NH:41][CH:42]([C:46]6[S:47][CH:48]=[CH:49][CH:50]=6)[NH:43][C:44](=[O:45])[C:39]=5[CH:38]=4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 117775245HCID 117775245, compound

Product 1

HCID 87055970HCID 87055970, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (150 mg, 0.30 mmol), compound 6-bromo-2-(thiophen-2-yl)-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one (112 mg, 0.36 mmol) and K3PO4.3H2O (239 mg, 0.90 mmol) in 1,4-dioxane (3 mL), Pd(dppf)Cl2 (20 mg) was added under N2 protection. After being stirred at 80° C. overnight, the reaction mixture was concentrated in vacuo, suspended in water and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by prep-HPLC to give the product of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4-oxo-2-(thiophen-2-yl)-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)benzofuran-3-carboxamide (40 mg, yield: 22%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.80 (d, J=1.6 Hz, 1H), 8.51 (d, J=4.4 Hz, 1H), 8.26 (d, J=2.0 Hz, 1H), 8.22 (s, 1H), 7.95˜8.05 (m, 4H), 7.60 (s, 1H), 7.47 (dd, J=5.2, 1.2 Hz, 1H), 7.41 (t, J=8.8 Hz, 2H), 7.12 (d, J=2.8 Hz, 1H), 7.00 (dd, J=4.8, 3.2 Hz, 1H), 6.14 (d, J=2.4 Hz, 1H), 3.14 (s, 3H), 2.98 (s, 3H), 2.83 (d, J=4.4 Hz, 3H). MS (M+H)+: 606

Workup

  1. additionwas added under N2 protection
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-21a3cf6eaa124326be7cfbb0e91e5f26
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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