N,N-Dimethylaniline → 8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-3-(2-hydroxyethyl)-7-methoxy-2H-chromen-2-one

HRID 20702Notes

Reaction equation

HRID 20702 reaction equation
CN(C)C1C=CC=CC=1.[Cl-].[Cl-].[Cl-].[Al+3].C([O:21][CH2:22][CH2:23][C:24]1[C:25](=[O:51])[O:26][C:27]2[C:32]([C:33]=1[NH:34][C:35]1[C:40]([Cl:41])=[CH:39][N:38]=[CH:37][C:36]=1[Cl:42])=[CH:31][CH:30]=[C:29]([O:43][CH3:44])[C:28]=2[O:45][CH:46]1[CH2:50][CH2:49][CH2:48][CH2:47]1)C1C=CC=CC=1>ClCCl>[CH:46]1([O:45][C:28]2[C:29]([O:43][CH3:44])=[CH:30][CH:31]=[C:32]3[C:27]=2[O:26][C:25](=[O:51])[C:24]([CH2:23][CH2:22][OH:21])=[C:33]3[NH:34][C:35]2[C:36]([Cl:42])=[CH:37][N:38]=[CH:39][C:40]=2[Cl:41])[CH2:50][CH2:49][CH2:48][CH2:47]1

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 6451240Aluminum(III) ChlorideHCID 866181393-(2-(benzyloxy)ethyl)-8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one

Product 1

HCID 248492588-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-3-(2-hydroxyethyl)-7-methoxy-2H-chromen-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N,N-Dimethylaniline (174 mg, 1.44 mmol) and aluminum trichloride (143 mg, 1.08 mmol) were sequentially added to a solution of 3-(2-(benzyloxy)ethyl)-8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (100 mg, 0.18 mmol) and dichloromethane (10 mL). The reaction was refluxed for 8 h, allowed to cool to rt, quenched with cold water (1 mL), and then poured into ice water (20 mL). The mixture was extracted with dichloromethane (15 mL×3), and the combined extracts were dried, filtered, concentrated, and purified by silica gel chromatography (ethyl acetate:petroleum ether) to give 8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-3-(2-hydroxyethyl)-7-methoxy-2H-chromen-2-one: 1H NMR (400 MHz, DMSO-d6): δ 9.26 (s, 1H), 8.47 (s, 2H), 6.94 (d, 1H), 6.85 (d, 1H), 5.58 (m, 1H), 4.83 (m, 1H), 3.81 (s, 3H), 3.60 (m, 2H), 2.68 (m, 2H), 1.90-1.50 (m, 8H); MS (ESI): 464.9.

Workup

  1. temperatureThe reaction was refluxed for 8 h
  2. customquenched with cold water (1 mL)
  3. additionpoured into ice water (20 mL)
  4. extractionThe mixture was extracted with dichloromethane (15 mL×3)
  5. customthe combined extracts were dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography (ethyl acetate:petroleum ether)

Sources & evidence

ORD record
ord-02a3853ad0284ff1a01b614492aea940
Source dataset
uspto-grants-2010_06
Patent number
US07745646B2

Reaction notes

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