Dimethyl Sulfoxide → 8-(6-chlorohexyloxy)-4-(3,5-dimethylpyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one

HRID 1095813Notes

Reaction equation

HRID 1095813 reaction equation
[CH3:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH3:23])[C:7]=1[NH:8][C:9]1[C:18]2[C:13](=[C:14]([OH:21])[C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[NH:12][C:11](=[O:22])[CH:10]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(C)=O.Br[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][Cl:41]>C(OCC)(=O)C>[Cl:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][O:21][C:14]1[C:15]([O:19][CH3:20])=[CH:16][CH:17]=[C:18]2[C:13]=1[NH:12][C:11](=[O:22])[CH:10]=[C:9]2[NH:8][C:7]1[C:6]([CH3:23])=[CH:5][N:4]=[CH:3][C:2]=1[CH3:1]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 10796Cesium carbonateHCID 805161-Bromo-6-chlorohexaneHCID 592681164-(3,5-dimethylpyridin-4-ylamino)-8-hydroxy-7-methoxyquinolin-2(1H)-one

Product 1

HCID 592681148-(6-chlorohexyloxy)-4-(3,5-dimethylpyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-(3,5-dimethylpyridin-4-ylamino)-8-hydroxy-7-methoxyquinolin-2(1H)-one (1.46 g, 4.7 mmol), cesium carbonate (1.83 g, 5.6 mmol), and DMSO (15 mL) was stirred at room temperature for 15min, and then 1-bromo-6-chlorohexane (0.83 mL, 5.6 mmol) was added. After 45 min, the reaction was diluted with ethyl acetate, washed with water (×3), dried, filtered, concentrated, and then triturated with hexane/diethyl ether to remove the excess 1-bromo-6-chlorohexane. The solid residue was purified by silica gel chromatography (49:1→23:2; dichloromethane/methanol) to give 8-(6-chlorohexyloxy)-4-(3,5-dimethylpyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one. 1H NMR (400 MHz, CDCl3): δ 8.59 (s, 1H), 8.38 (s, 2H), 7.42 (d, 1H), 6.90 (d, 1H), 6.05 (s, 1H), 5.13 (d, 1H), 4.12 (t, 2H), 3.97 (s, 3H), 3.56 (t, 2H), 2.21 (s, 6H), 1.82 (m, 4H), 1.52 (m, 4H); MS (ESI): 430.3.

Workup

  1. waitAfter 45 min
  2. washwashed with water (×3)
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customtriturated with hexane/diethyl ether
  7. customto remove the excess 1-bromo-6-chlorohexane
  8. customThe solid residue was purified by silica gel chromatography (49:1→23:2; dichloromethane/methanol)

Sources & evidence

ORD record
ord-e7026a994111449a8ea181c3127bd478
Source dataset
uspto-grants-2012_03
Patent number
US08138205B2

Reaction notes

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