Tetrahydrofuran → Ethyl 4-{[2-(methylsulfanyl)pyrimidin-5-yl]methyl}quinoline-2-carboxylate

HRID 1497331Notes

Reaction equation

HRID 1497331 reaction equation
CC1(C)C(C)(C)OB([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:10]=2)O1.Br[CH2:26][C:27]1[CH:28]=[N:29][C:30]([S:33][CH3:34])=[N:31][CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1COCC1>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].C(Cl)Cl.O>[CH3:34][S:33][C:30]1[N:31]=[CH:32][C:27]([CH2:26][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:10]=2)=[CH:28][N:29]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 60209908Ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline-2-carboxylateHCID 60209911HCID 60209911, compound

Product 1

HCID 60209912Ethyl 4-{[2-(methylsulfanyl)pyrimidin-5-yl]methyl}quinoline-2-carboxylate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
77 °C

Procedure

In a microwave vial containing ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline-2-carboxylate (K4) (0.15 g, 0.46 mmol), 5-(bromomethyl)-2-(methylsulfanyl)pyrimidine (N3) (0.12 g, 0.55 mmol), cesium carbonate (0.45 g, 1.4 mmol), and PdCl2(dppf)-CH2Cl2 adduct (0.037 g, 0.05 mmol) was added 4.1 mL THF and 0.41 mL water. The reaction mixture was heated to 77° C. for 1 h. The reaction mixture was cooled to room temperature, quenched with water, extracted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered, and concentrated. The resultant residue was subjected to silica gel chromatography eluting with 0-70% ethyl acetate in hexanes to afford ethyl 4-{[2-(methylsulfanyl)pyrimidin-5-yl]methyl}quinoline-2-carboxylate (N4) that gave a mass ion (ES+) of 340.3 for M+H+. The above compound was converted to the titled compound by the procedure described in Example 11 that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 411.1481 for M+H30 . 1H NMR (400 MHz, CDCl3) δ 8.42 (s, 2H), 8.37 (d, J=6.4 Hz, 1H), 8.19 (d, J=8.2 Hz, 1H), 8.14 (s, 1H), 7.99 (d, J=8.4 Hz, 1H), 7.84-7.80 (m, 1H), 7.70-7.66 (m, 1H), 4.44 (s, 2H), 4.13 (dd, J=4.9, 11.2 Hz, 1H), 4.08-4.00 (m, 2H), 3.77-3.71 (m, 1H), 3.55-3.49 (m, 1H), 3.30-3.25 (m, 1H), 2.54 (s, 3H), 2.15-2.11 (m, 1H) 1.95-1.85 (m, 1H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with water
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washeluting with 0-70% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-152cef85e598459bb67cfe31177e127f
Source dataset
uspto-grants-2015_12
Patent number
US09199939B2

Reaction notes

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