Sodium hydride → 3-(2-(benzyloxy)ethyl)-8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one

HRID 20701Notes

Reaction equation

HRID 20701 reaction equation
[H-].[Na+].[NH2:3][C:4]1[C:13]2[C:8](=[C:9]([O:16][CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[O:7][C:6](=[O:22])[C:5]=1[CH2:23][CH2:24][O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[Cl:33][C:34]1[CH:35]=[N:36][CH:37]=[C:38]([Cl:41])[C:39]=1Cl>CS(C)=O>[CH2:26]([O:25][CH2:24][CH2:23][C:5]1[C:6](=[O:22])[O:7][C:8]2[C:13]([C:4]=1[NH:3][C:39]1[C:38]([Cl:41])=[CH:37][N:36]=[CH:35][C:34]=1[Cl:33])=[CH:12][CH:11]=[C:10]([O:14][CH3:15])[C:9]=2[O:16][CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 37865313,4,5-TrichloropyridineHCID 866181384-amino-3-(2-(benzyloxy)ethyl)-8-(cyclopentyloxy)-7-methoxy-2H-chromen-2-one

Product 1

HCID 866181393-(2-(benzyloxy)ethyl)-8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

Sodium hydride (230 mg, 60%, 5.8 mmol) was added portionwise to a solution of 4-amino-3-(2-(benzyloxy)ethyl)-8-(cyclopentyloxy)-7-methoxy-2H-chromen-2-one (800 mg, 1.86 mmol) and DMSO (20 mL). After 10 min at rt, 3,4,5-trichloropyridine (1.0 g, 5.47 mmol) was added. The reaction was then heated at 50° C. overnight, allowed to cool to rt, quenched with drops of water, poured into 0.5M KH2PO4 (15 mL), and then extracted with ethyl acetate (50 mL×2). The combined extracts were washed with brine (50 mL), dried, filtered, concentrated, and purified by silica gel chromatography (ethyl acetate:petroleum ether) to give 3-(2-(benzyloxy)ethyl)-8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one.

Workup

  1. temperatureto cool to rt
  2. customquenched with drops of water
  3. additionpoured into 0.5M KH2PO4 (15 mL)
  4. extractionextracted with ethyl acetate (50 mL×2)
  5. washThe combined extracts were washed with brine (50 mL)
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography (ethyl acetate:petroleum ether)

Sources & evidence

ORD record
ord-98d729acf09d46c1a839342fefd7777f
Source dataset
uspto-grants-2010_06
Patent number
US07745646B2

Reaction notes

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