Sodium Carbonate → 1-(2-(7-Methoxyquinolin-4-yloxy)ethyl)-5-(thiophen-2-yl)pyridin-2(1H)-one

HRID 1878691Notes

Reaction equation

HRID 1878691 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[CH:13][CH:12]=2)[CH:7]=1.[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:22][O:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([O:10][CH2:9][CH2:8][N:6]3[CH:7]=[C:2]([C:25]4[S:24][CH:28]=[CH:27][CH:26]=4)[CH:3]=[CH:4][C:5]3=[O:23])=[CH:12][CH:13]=[N:14]2)=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 248844955-Bromo-1-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-one

Product 1

HCID 250171031-(2-(7-Methoxyquinolin-4-yloxy)ethyl)-5-(thiophen-2-yl)pyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 5-bromo-1-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-one (50 mg, 133 μmol), thiophene-2-boronic acid (34 mg, 267 μmol), 1,1′-bis(diphenylphosphino)ferrocene]dichloride palladium(II) (8 mg, 11 μmol), and Na2CO3 (2M, 200 μl, 400 μmol) in DME (0.5 mL) were heated to 85° C. for 1 h. The reaction mixture was partitioned between CH2Cl2 (10 mL) and 5% NaHCO3 (5 mL). The aqueous layer was further extracted with CH2Cl2 (5 mL) and the combined organics were dried with brine and MgSO4. The concentrated organic residue was purified on 4 g silica eluting with 0-2.5% MeOH/CH2Cl2. The product was isolated as an off white solid. MS (ESI pos. ion) m/z (MH+): 379. Calc'd exact mass for C21H18N2O3S: 378. 1H NMR (400 MHz, Chloroform-d) δ ppm 3.92 (s, 3H) 4.53 (s, 4H) 6.62-6.67 (m, 2H) 7.24-7.28 (m, 1H) 7.34 (d, J=2.54 Hz, 1H) 7.63 (dd, J=9.49, 2.64 Hz, 1H) 7.79 (d, J=2.54 Hz, 1H) 8.00 (d, J=9.19 Hz, 1H) 8.66 (d, J=5.28 Hz, 1H)

Workup

  1. customThe reaction mixture was partitioned between CH2Cl2 (10 mL) and 5% NaHCO3 (5 mL)
  2. extractionThe aqueous layer was further extracted with CH2Cl2 (5 mL)
  3. dry with materialthe combined organics were dried with brine and MgSO4
  4. customThe concentrated organic residue was purified on 4 g silica eluting with 0-2.5% MeOH/CH2Cl2
  5. customThe product was isolated as an off white solid

Sources & evidence

ORD record
ord-9396a98586504178bb9d1b2dc7b9c0be
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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