Dimethyl Sulfoxide → 4-(3-bromo-5-chloropyridin-4-ylamino)-8-(cyclopentyloxy)-7-methoxy-2H-chromen-2-one

HRID 20640Notes

Reaction equation

HRID 20640 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])[CH:5]=1.CS(C)=O.[Br:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([Cl:35])[C:33]=1Cl>[Cl-].[Na+].O>[Br:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([Cl:35])[C:33]=1[NH: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])[CH:5]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 687426533-Bromo-4,5-dichloropyridineHCID 771747934-amino-8-(cyclopentyloxy)-7-methoxy-2H-chromen-2-one

Product 1

HCID 248494324-(3-bromo-5-chloropyridin-4-ylamino)-8-(cyclopentyloxy)-7-methoxy-2H-chromen-2-one

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

Sodium hydride (7 mg, 60%, 0.18 mmol) was added to a solution of 4-amino-8-(cyclopentyloxy)-7-methoxy-2H-chromen-2-one (77 mg, 0.28 mmol, Example 3, Step 1) and anhydrous DMSO (3 mL) under N2. After 10 min, 3-bromo-4,5-dichloropyridine (69 mg, 0.31 mmol) was added, and the reaction was stirred for 20 h, poured into brine, and extracted with EtOAc. The organic extract was dried, filtered, concentrated, and purified by reverse-phase HPLC (20→100% MeCN/H2O) to give 4-(3-bromo-5-chloropyridin-4-ylamino)-8-(cyclopentyloxy)-7-methoxy-2H-chromen-2-one: 1H NMR (400 MHz, DMSO-d6): δ 9.54 (s, 1H), 8.91 (s, 1H), 8.84 (s, 1H), 7.95 (d, 1H), 7.21 (d, 1H), 4.85 (m, 1H), 4.59 (s, 1H), 3.92 (s, 3H), 1.87-1.79 (m, 4H), 1.68-1.54 (m, 4H); MS (ESI): 464.7.

Workup

  1. extractionextracted with EtOAc
  2. extractionThe organic extract
  3. customwas dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by reverse-phase HPLC (20→100% MeCN/H2O)

Sources & evidence

ORD record
ord-dccd032796f642beb0e66a4b9d608b32
Source dataset
uspto-grants-2010_06
Patent number
US07745646B2

Reaction notes

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