Cesium carbonate → 6-{4-[(3-cyclopropylpyridin-2-yl)oxy]-2-methylphenyl}-1,5-dimethyl-3-{[2-(trimethylsilyl)ethoxy]methyl}pyrimidine-2,4(1H,3H)-dione

HRID 2281928Notes

Reaction equation

C(P(C(C)(C)C)C1C(C)=C(C)C(C)C(C)(C(C)C)C=1C1C=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl[C:36]1[C:41]([CH:42]2[CH2:44][CH2:43]2)=[CH:40][CH:39]=[CH:38][N:37]=1.[OH:45][C:46]1[CH:51]=[CH:50][C:49]([C:52]2[N:57]([CH3:58])[C:56](=[O:59])[N:55]([CH2:60][O:61][CH2:62][CH2:63][Si:64]([CH3:67])([CH3:66])[CH3:65])[C:54](=[O:68])[C:53]=2[CH3:69])=[C:48]([CH3:70])[CH:47]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:42]1([C:41]2[C:36]([O:45][C:46]3[CH:51]=[CH:50][C:49]([C:52]4[N:57]([CH3:58])[C:56](=[O:59])[N:55]([CH2:60][O:61][CH2:62][CH2:63][Si:64]([CH3:67])([CH3:66])[CH3:65])[C:54](=[O:68])[C:53]=4[CH3:69])=[C:48]([CH3:70])[CH:47]=3)=[N:37][CH:38]=[CH:39][CH:40]=2)[CH2:44][CH2:43]1

Participants

Conditions

Temperature: 120 °C

Procedure

Palladium(II) acetate (61 mg, 0.27 mmol) and di-tert-butyl[3,4,5,6-tetramethyl-2′,4′,6-tri(propan-2-yl)biphenyl-2-yl]phosphane (130 mg, 0.27 mmol) were added to a mixture of C6 (615 mg, 4.00 mmol), C5 (1.0 g, 2.6 mmol) and cesium carbonate (2.6 g, 8.0 mmol) in 1,4-dioxane (25 mL). The reaction mixture was stirred at 120° C. under microwave irradiation for 5 hours, then diluted with ethyl acetate (50 mL) and filtered. After removal of solvents in vacuo, the residue was purified via silica gel chromatography (Gradient: 0% to 25% ethyl acetate in petroleum ether) to provide the product as a yellow gum. Yield: 900 mg, 1.8 mmol, 69%. LCMS m/z 494.1 [m+H]+. 1H NMR (400 MHz, CDCl3) δ 8.02 (dd, J=4.8, 1.8 Hz, 1H), 7.30 (dd, J=7.4, 1.8 Hz, 1H), 7.11-7.14 (m, 1H), 7.08-7.10 (m, 2H), 7.01 (dd, J=7.5, 4.8 Hz, 1H), 5.51 (AB quartet, JAB=9.3 Hz, ΔνAB=3.8 Hz, 2H), 3.74-3.80 (m, 2H), 3.08 (5, 3H), 2.18 (5, 3H), 2.16-2.24 (m, 1H), 1.70 (5, 3H), 1.00-1.06 (m, 4H), 0.74-0.79 (m, 2H), 0.03 (5, 9H).

Workup

filtrationfiltered
customAfter removal of solvents in vacuo
customthe residue was purified via silica gel chromatography (Gradient: 0% to 25% ethyl acetate in petroleum ether)

Sources & evidence

ORD record: ord-2cb6005971154903a117630ad7b53efa
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139561B2

Reaction notes

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