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

HRID 1095790Notes

Reaction equation

HRID 1095790 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl: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]([Cl:23])=[CH:5][N:4]=[CH:3][C:2]=1[Cl:1]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 10796Cesium carbonateHCID 805161-Bromo-6-chlorohexaneHCID 592681184-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxyquinolin-2(1H)-one2×

Product 1

HCID 592681178-(6-chlorohexyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-oneYield 71.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxyquinolin-2(1H)-one (Intermediate 3) (19.9 g, 56.5 mmol), cesium carbonate (36.9 g, 113 mmol), and DMSO (190 mL) was heated at 30° C. for 15, minutes, and then 1-bromo-6-chlorohexane (12.4 g, 62.2 mmol) was added. The reaction was heated at 30° C. for 4.5 h, diluted with ethyl acetate (2 L), washed with 1M pH 7 phosphate buffer (2 L), and then washed with water (2L×2). The organic layer was dried, filtered, concentrated, and then purified by silica gel chromatography (100% ethyl acetate) to give 19 g of 8-(6-chlorohexyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 10.01 (s, 1H), 8.87 (s, 1H), 8.79 (s, 2H), 7.90 (d, 1H), 7.06 (d, 1H), 4.80 (s, 1H), 3.98 (t, 2H), 3.92 (s, 3H), 3.65 (t, 2H), 1.77 (m, 4H), 1.43 (m, 4H); MS (ESI): 470.3.

Workup

  1. temperatureThe reaction was heated at 30° C. for 4.5 h
  2. washwashed with 1M pH 7 phosphate buffer (2 L)
  3. washwashed with water (2L×2)
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography (100% ethyl acetate)

Sources & evidence

ORD record
ord-73f57a325548462285faec981dcb5bc8
Source dataset
uspto-grants-2012_03
Patent number
US08138205B2

Reaction notes

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