Sodium Carbonate → HCID 57529013, compound

HRID 1454045Notes

Reaction equation

HRID 1454045 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH2:16][CH2:17][C:18]3[N:19]=[C:20]([C:24]4[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=4)[O:21][C:22]=3[CH3:23])=[CH:12][CH:13]=2)[CH2:8][CH2:7]1)[CH3:2].[CH3:32][O:33][C:34]1[N:39]=[C:38]([O:40][CH3:41])[C:37](B(O)O)=[CH:36][N:35]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O1CCOCC1.[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Fe+2].Cl[Pd]Cl>[CH2:1]([O:3][C:4](=[O:31])[CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH2:16][CH2:17][C:18]3[N:19]=[C:20]([C:24]4[CH:29]=[CH:28][C:27]([C:37]5[C:38]([O:40][CH3:41])=[N:39][C:34]([O:33][CH3:32])=[N:35][CH:36]=5)=[CH:26][CH:25]=4)[O:21][C:22]=3[CH3:23])=[CH:12][CH:13]=2)[CH2:8][CH2:7]1)[CH3:2]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2736209(2,4-Dimethoxypyrimidin-5-yl)boronic acidHCID 69053646(1S)-(5-{2-[2-(4-bromo-phenyl)-5-methyl-oxazole-4-yl]-ethoxy}-indan-1-yl)-acetic acid ethyl ester

Product 1

HCID 57529013HCID 57529013, compoundYield 45%

Reagents, catalysts & solvents 4

HCID 7611Bis(eta-cyclopentadienyl) ironCatalystHCID 24290Palladium ChlorideCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution containing (1S)-(5-{2-[2-(4-bromo-phenyl)-5-methyl-oxazole-4-yl]-ethoxy}-indan-1-yl)-acetic acid ethyl ester (0.100 g, 0.21 mmol), 1,1′-phosphino)ferrocene]dichloro palladium(II) (16.9 mg, 0.02 mmol), and 2,4-dimethoxy-pyrimidin-5-boronic acid (0.076 g, 0.41 mmol) in degassed toluene and dioxane (4:1, 2 mL) was added aqueous 2 M sodium carbonate (0.5 mL). The mixture was heated at 85° C. for 16 hours. The reaction mixture was cool to rt and concentrated under vacuum and the residue was dissolved in methanol and acetonitrile and filtered through a C8 reverse phase extraction cartridge. The filtrated concentrated and the residue was purified by preparative HPLC to obtain [(1S)-5-(2-{2-[4-(2,4-dimethoxy-pyrimidin-5-yl)-phenyl]-5-methyl-oxazol-4-yl}-ethoxy)-indan-1-yl]-acetic acid ethyl ester in 45% yield, (50 mg, 0.09 mmol). 1H NMR (CD3Cl) δ 1.3 (t, 3H), 1.8 (m, 1H), 2.4 (m, 5H), 2.9 (m, 3H) 3.1 (t, 2H), 3.5 (m, 1H), 4.1 (s, 6H), 4.2 (m, 4H), 6.7 (m, 2H), 7.1 (d, 1H) 7.8 (d, 2H), 8.4 (s, 1H); MS (ES) 544 (M+1)+.

Workup

  1. temperatureThe reaction mixture was cool to rt
  2. concentrationconcentrated under vacuum
  3. dissolutionthe residue was dissolved in methanol
  4. filtrationacetonitrile and filtered through a C8 reverse phase extraction cartridge
  5. concentrationThe filtrated concentrated
  6. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-d480395294bd4c33b947fbe517edda00
Source dataset
uspto-grants-2009_01
Patent number
US07476742B2

Reaction notes

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