Sodium Carbonate → 2-(5,6-difluoro-2'-oxo-4'-pyrimidin-5-ylspiro[1-benzofuran-3,3'-indol]-1'(2' H)-yl)-N-(2-fluorophenyl)acetamide

HRID 645196Notes

Reaction equation

HRID 645196 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:26]3[CH:27]=[C:28]([F:32])[C:29]([F:31])=[CH:30][C:25]=3[O:24][CH2:23]1)[C:5](=[O:22])[N:6]2[CH2:11][C:12]([NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[F:21])=[O:13].[N:33]1[CH:38]=[C:37](B(O)O)[CH:36]=[N:35][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:32][C:28]1[C:29]([F:31])=[CH:30][C:25]2[O:24][CH2:23][C:4]3([C:3]4[C:7](=[CH:8][CH:9]=[CH:10][C:2]=4[C:37]4[CH:38]=[N:33][CH:34]=[N:35][CH:36]=4)[N:6]([CH2:11][C:12]([NH:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[F:21])=[O:13])[C:5]3=[O:22])[C:26]=2[CH:27]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 592635092-(4'-bromo-5,6-difluoro-2'-oxospiro[1-benzofuran-3,3'-indol]-1'(2' H)-yl)-N-(2-fluorophenyl)acetamide

Product 1

HCID 592635142-(5,6-difluoro-2'-oxo-4'-pyrimidin-5-ylspiro[1-benzofuran-3,3'-indol]-1'(2' H)-yl)-N-(2-fluorophenyl)acetamideYield 86.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-(4′-bromo-5,6-difluoro-2′-oxospiro[1-benzofuran-3,3′-indol]-1′(2′ H)-yl)-N-(2-fluorophenyl)acetamide (0.15 g, 0.30 mmol) in anhydrous 1,4-dioxane (5.00 mL) was added Pd(PPh3)4 (0.03 g, 0.03 mmol) and stirred at ambient temperature for 10 min. Pyrimidine-5-boronic acid (0.06 g, 0.45 mmol) and sodium carbonate (0.90 mL of 2 M solution, 1.80 mmol) were added. The reaction mixture was reluxed at 120° C. for 16 h, diluted with ethyl acetate (50.0 mL). The organic layer was washed with water, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/hexane, 1/1) to give the title compound (0.13 g, 84%): 1H NMR (300 MHz, CDCl3) δ 9.13 (s, 1H), 8.29-8.10 (m, 3H), 7.62 (s, 1H), 7.44 (t, 1H), 7.16-7.03 (m, 4H), 6.91 (d, 1H), 6.85-6.76 (m, 1H), 6.46-6.37 (m, 1H), 4.85-4.73 (m, 2H), 4.61-4.47 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 177.1, 163.9, 157.7, 156.4, 155.7, 141.9, 132.9, 130.0, 126.0, 124.7, 121.9, 115.0, 111.6, 109.8, 100.2, 79.4, 57.9, 44.7; MS (ES+) m/z 503.5 (M+1).

Workup

  1. waitThe reaction mixture was reluxed at 120° C. for 16 h
  2. washThe organic layer was washed with water
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-dcc00d2b442149f5a6bd2e76bd745082
Source dataset
uspto-grants-2010_04
Patent number
US07700641B2

Reaction notes

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