Sodium Carbonate → HCID 87054907, compound

HRID 2201577Notes

Reaction equation

HRID 2201577 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]=[CH:7][N:6]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=1)[C:5]2=[O:19].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]3[CH:39]=[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[C:37](B4OC(C)(C)C(C)(C)O4)=[CH:36][C:30]=3[C:31]=2[C:32]([NH:34][CH3:35])=[O:33])=[CH:23][CH:22]=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:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]3[CH:39]=[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:42])=[O:43])[C:37]([C:2]4[N:3]=[C:4]5[C:9](=[N:10][CH:11]=4)[N:8]=[CH:7][N:6]([C:12]4[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=4)[C:5]5=[O:19])=[CH:36][C:30]=3[C:31]=2[C:32]([NH:34][CH3:35])=[O:33])=[CH:23][CH:22]=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 117771835HCID 117771835, compound

Product 1

HCID 87054907HCID 87054907, compoundYield 65.5%

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
120 °C

Procedure

To a stirring mixture of 6-bromo-3-(3-fluorophenyl)pteridin-4(3H)-one (32 mg, 0.099 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (50 mg, 0.099 mmol) and Na2CO3 (18 mg, 0.199 mmol) in dioxane/H2O (1 mL/0.1 mL) was added Pd(dppf)Cl2 (10 mg) under N2 protection. The mixture was stirred in a pre-heated oil-bath at 120° C. for 5 h. The mixture was cooled and extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered and evaporated. The crude product was purified by prep-HPLC to give the pure product of 2-(4-fluorophenyl)-5-(3-(3-fluorophenyl)-4-oxo-3,4-dihydropteridin-6-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (40 mg, yield: 50%). 1H-NMR (CDCl3, 400 MHz) δ 9.20 (s, 1H), 8.36 (s, 1H), 8.13 (s, 1H), 7.87˜7.92 (m, 2H), 7.63 (s, 1H), 7.43˜7.55 (m, 1H), 7.33˜7.38 (m, 1H), 7.13˜7.25 (m, 4H), 6.07 (br s, 1H), 3.30 (s, 3H), 2.94 (d, J=4.8 Hz, 3H), 2.86 (s, 3H). MS (M+H)+: 617.

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with EtOAc
  3. washThe combined organic phases were 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-7dfa76d81b8f4daa900e44802de35f7c
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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