Dimethyl Sulfoxide → 8-(cyclopentyloxy)-4-(2,6-dichlorophenylamino)-7-methoxy-2H-chromen-2-one

HRID 20628

Reaction equation

HRID 20628 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:5]=1[NH2:6].CS(C)=O.CC1C=CC(S(O[C:27]2[C:36]3[C:31](=[C:32]([O:39][CH:40]4[CH2:44][CH2:43][CH2:42][CH2:41]4)[C:33]([O:37][CH3:38])=[CH:34][CH:35]=3)[O:30][C:29](=[O:45])[CH:28]=2)(=O)=O)=CC=1>OP([O-])(O)=O.[K+]>[CH:40]1([O:39][C:32]2[C:33]([O:37][CH3:38])=[CH:34][CH:35]=[C:36]3[C:31]=2[O:30][C:29](=[O:45])[CH:28]=[C:27]3[NH:6][C:5]2[C:4]([Cl:3])=[CH:10][CH:9]=[CH:8][C:7]=2[Cl:11])[CH2:41][CH2:42][CH2:43][CH2:44]1

Participants

6

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 118462,6-DichloroanilineHCID 24758Sodium hydrideHCID 866181328-(cyclopentyloxy)-7-methoxy-2-oxo-2H-chromen-4-yl 4-methylbenzenesulfonate

Product 1

HCID 248493788-(cyclopentyloxy)-4-(2,6-dichlorophenylamino)-7-methoxy-2H-chromen-2-one

Reagents, catalysts & solvents 1

HCID 516951Monobasic potassium phosphateSolvent

Conditions

Temperature
50 °C

Procedure

Sodium hydride (10 mg, 60%, 0.25 mmol) was added to a solution of 2,6-dichloroaniline (40 mg, 0.25 mmol) and anhydrous DMSO (2 mL) at rt under N2. After 40 min, this mixture was added to a solution of 8-(cyclopentyloxy)-7-methoxy-2-oxo-2H-chromen-4-yl 4-methylbenzenesulfonate (70 mg, 0.16 mmol) and anhydrous DMSO (2 mL) at rt under N2. After 1.5 h at rt, the reaction was heated at 50° C. After an additional 1.5 h, a second aliquot of the sodium 2,6-dichloroanilide mixture was added. After an additional hour, the reaction was allowed to cool to rt, diluted with 1M KH2PO4 (40 mL), and extracted with ethyl acetate (40 mL×2). The combined extracts were dried, filtered, concentrated, and purified by silica gel chromatography (4:1→3:2; hexanes:ethyl acetate) to give 8-(cyclopentyloxy)-4-(2,6-dichlorophenylamino)-7-methoxy-2H-chromen-2-one: 1H NMR (400 MHz, DMSO-d6): δ 9.39 (s, 1H), 7.95 (d, 1H), 7.69 (d, 2H), 7.50 (t, 1H), 7.18 (d, 1H), 4.83 (m, 1H), 4.36 (s, 1H), 3.90 (s, 3H), 1.80-1.00 (m, 8H); MS (ESI): 419.9.

Workup

  1. waitAfter 1.5 h at rt
  2. waitAfter an additional 1.5 h
  3. waitAfter an additional hour
  4. temperatureto cool to rt
  5. extractionextracted with ethyl acetate (40 mL×2)
  6. customThe combined extracts were dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography (4:1→3:2; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-7b6c0f8b459e46818dbbcfda13ea9669
Source dataset
uspto-grants-2010_06
Patent number
US07745646B2

Linked notes

Loading…