4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxy-2H-chromen-2-one → (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate

HRID 20681Notes

Reaction equation

HRID 20681 reaction equation
[C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8](OC(=N)C(Cl)(Cl)Cl)[O:7][CH:6]1[CH2:26][O:27][C:28](=[O:30])[CH3:29])(=[O:3])[CH3:2].[Cl:31][C:32]1[CH:33]=[N:34][CH:35]=[C:36]([Cl:53])[C:37]=1[NH:38][C:39]1[C:48]2[C:43](=[C:44]([OH:51])[C:45]([O:49][CH3:50])=[CH:46][CH:47]=2)[O:42][C:41](=[O:52])[CH:40]=1>C(#N)C>[C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@H:8]([O:51][C:44]2[C:45]([O:49][CH3:50])=[CH:46][CH:47]=[C:48]3[C:43]=2[O:42][C:41](=[O:52])[CH:40]=[C:39]3[NH:38][C:37]2[C:36]([Cl:53])=[CH:35][N:34]=[CH:33][C:32]=2[Cl:31])[O:7][C@@H:6]1[CH2:26][O:27][C:28](=[O:30])[CH3:29])(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 248495704-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxy-2H-chromen-2-oneHCID 68741859HCID 68741859, compound

Product 1

HCID 24849804(2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Boron trifluoride•OEt2 (54 μL, 0.43 mmol) was added to a suspension of (3R,4S,5S,6R)-2-(acetoxymethyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (0.168 g, 0.341 mmol), 4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxy-2H-chromen-2-one (60 mg, 0.17 mmol, Example 29), and anhydrous acetonitrile (2 mL) at −40° C. under N2. After 2 h at −40° C., the reaction was allowed to warm to rt and stirred overnight. The mixture was concentrated and purified by reverse-phase HPLC to give (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate: 1H NMR (400 MHz, DMSO-d6): δ 9.55 (s, 1H), 8.83 (s, 2H), 8.03 (d, 1H), 7.25 (d, 1H), 5.34 (m, 2H), 5.08 (m, 1H), 4.98 (m, 1H), 4.67 (s, 1H), 4.12 (m, 1H), 3.99 (m, 2H), 3.91 (s, 3H), 2.06 (s, 3H), 1.98 (m, 6H), 1.94 (s, 3H); MS (ESI): 682.8.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-2410da5c9c7846a5a29622c1be2c59a6
Source dataset
uspto-grants-2010_06
Patent number
US07745646B2

Reaction notes

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