Sodium Carbonate → HCID 136339016, compound

HRID 2201572Notes

Reaction equation

HRID 2201572 reaction equation
C([C:3]1[NH:12][C:11](=[O:13])[C:10]2[C:5](=[N:6][CH:7]=[C:8](Br)[N:9]=2)[N:4]=1)C.[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[O:23][C:24]3[CH:34]=[C:33]([N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37])[C:32](B4OC(C)(C)C(C)(C)O4)=[CH:31][C:25]=3[C:26]=2[C:27]([NH:29][CH3:30])=[O:28])=[CH:18][CH:17]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[O:23][C:24]3[CH:34]=[C:33]([N:35]([CH3:40])[S:36]([CH3:39])(=[O:37])=[O:38])[C:32]([C:8]4[N:9]=[C:10]5[C:5](=[N:6][CH:7]=4)[N:4]=[CH:3][NH:12][C:11]5=[O:13])=[CH:31][C:25]=3[C:26]=2[C:27]([NH:29][CH3:30])=[O:28])=[CH:18][CH:17]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 137001383HCID 137001383, compound

Product 1

HCID 136339016HCID 136339016, compoundYield 26.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

To a stirring mixture of ethyl 6-bromopteridin-4(3H)-one (50 mg, 0.22 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (110 mg, 0.22 mmol) and Na2CO3 (35 mg, 0.33 mmol) in dioxane/H2O (2 mL/0.2 mL) was added Pd(dppf)Cl2 (10 mg) under N2 protection. The mixture was stirred at 100° C. overnight. The mixture was concentrated in vacuo and extracted with EtOAc. After the organic layer was washed with brine, dried over Na2SO4, filtered and evaporated, the crude product was purified by prep-HPLC to give the product of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4-oxo-3,4-dihydropteridin-6-yl)benzofuran-3-carboxamide (30 mg, yield: 26%). 1H-NMR (DMSO-d6, 400 MHz) δ 9.19 (s, 1H), 8.61 (d, J=4.8 Hz, 1H), 8.39 (s, 1H), 8.19 (s, 1H), 7.97˜7.99 (m, 3H), 7.42 (t, J=8.4 Hz, 2H), 3.37 (s, 3H), 3.00 (s, 3H), 2.83 (d, J=4.0 Hz, 3H). MS (M+H)+: 523.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. extractionextracted with EtOAc
  3. washAfter the organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customthe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-fa85618850dc4bfbb09682eabf508858
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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