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

HRID 1878700Notes

Reaction equation

HRID 1878700 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5](=[O:24])[N:6]([CH2:8][CH:9]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:22][CH3:23])=[CH:19][CH:20]=3)[N:15]=[CH:14][CH:13]=2)[CH3:10])[CH:7]=1.[S:25]1[CH:29]=[CH:28][CH:27]=[C:26]1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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]>[CH3:23][O:22][C:18]1[CH:17]=[C:16]2[C:21]([C:12]([O:11][CH:9]([CH3:10])[CH2:8][N:6]3[CH:7]=[C:2]([C:26]4[S:25][CH:29]=[CH:28][CH:27]=4)[CH:3]=[CH:4][C:5]3=[O:24])=[CH:13][CH:14]=[N:15]2)=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 598430605-Bromo-1-(2-(7-methoxyquinolin-4-yloxy)propyl)pyridin-2(1H)-one

Product 1

HCID 250186391-(2-(7-Methoxyquinolin-4-yloxy)propyl)-5-(thiophen-2-yl)pyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 5-bromo-1-(2-(7-methoxyquinolin-4-yloxy)propyl)pyridin-2(1H)-one (20 mg, 51 μmol), thiophen-2-ylboronic acid (13 mg, 103 μmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (2 mg, 3 μmol), and Na2CO3 (77 μl, 154 μmol) in DME (0.5 mL) was heated to 80° C. for 2 h. The mixture was purified on RP-HPLC and the product was netralized with CH2Cl2/NaOH (1 M). The product was lyophilized from 1:1 acetonitrile/water (1 mL) to give a white fluffy powder. MS (ESI pos. ion) m/z (MH+): 393. Calc'd exact mass for C22H20N2O3S: 392. 1H NMR (400 MHz, Chloroform-d) δ ppm 1.55 (d, J=6.02 Hz, 3H) 3.49 (d, J=3.01 Hz, 1H) 3.91 (s, 3H) 4.03 (dd, J=13.55, 8.03 Hz, 1H) 4.58 (dd, J=13.55, 3.01 Hz, 1H) 5.10-5.22 (m, 1H) 6.58 (d, J=9.54 Hz, 1H) 6.66 (d, J=5.02 Hz, 1H) 6.88 (d, J=3.01 Hz, 1H) 6.96-7.01 (m, 1H) 7.05 (dd, J=9.03, 2.51 Hz, 1H) 7.19 (d, J=5.02 Hz, 1H) 7.30 (d, J=2.01 Hz, 1H) 7.52 (dd, J=9.54, 2.51 Hz, 1H) 7.63 (d, J=2.51 Hz, 1H) 8.05 (d, J=9.03 Hz, 1H) 8.59 (d, J=5.52 Hz, 1H). 13C NMR (101 MHz, Chloroform-d) δ ppm 17.37, 53.44, 55.03, 55.49, 71.85, 100.05, 107.33, 114.41, 116.10, 118.50, 120.89, 122.78, 124.20, 127.97, 135.11, 138.95, 139.26, 151.43, 151.71, 160.01, 160.98, 161.84.

Workup

  1. customThe mixture was purified on RP-HPLC
  2. customto give a white fluffy powder

Sources & evidence

ORD record
ord-f20cba035ae04917acfdd94c7014adfe
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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