Water → HCID 67618429, compound

HRID 862487Notes

Reaction equation

HRID 862487 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH2:15][O:16][CH3:17])([CH2:12][O:13][CH3:14])[C@@H:9]([OH:18])[C@H:8]([NH:19][C:20]3[CH:25]=[CH:24][C:23](=[O:26])[NH:22][N:21]=3)[C:7]=2[CH:27]=1)#[N:2].[Cl:28][CH2:29][C:30]#[C:31][CH2:32]Cl.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH2:12][O:13][CH3:14])([CH2:15][O:16][CH3:17])[C@@H:9]([OH:18])[C@H:8]([NH:19][C:20]3[CH:25]=[CH:24][C:23](=[O:26])[N:22]([CH2:32][C:31]#[C:30][CH2:29][Cl:28])[N:21]=3)[C:7]=2[CH:27]=1)#[N:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 131821,4-Dichloro-2-butyneHCID 10714321HCID 10714321, compound

Product 1

HCID 67618429HCID 67618429, compoundYield 24.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(-)-(3S,4R)-6-Cyano-3,4-dihydro-4-[(1,6-dihydro-6-oxo-3-pyridazinyl)amino]-2,2-bis(methoxymethyl)-2H-1-benzopyran-3-ol (556 mg, 1.5 mmol) obtained in Example 8 and 1,4-dichloro-2-butyne (2.9 ml, 30 mmol) were dissolved in dimethylformamide (10 ml). Potassium carbonate (413 mg) was added and the mixture was reacted at 120° C. overnight. Water was added to the reaction mixture and the mixture was extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure. The residue obtained was purified by silica gel column chromatography (methanol:chloroform=1:30) to give 171 mg of crude (3S,4R)-6-cyano-4-[(1-(4-chloro-2-butyn-1-yl)-1,6-dihydro-6-oxo-3-pyridazinyl)amino]-3,4-dihydro-2,2-bis(methoxymethyl)-2H-1-benzopyran-3-ol. The compound was dissolved in dimethylformamide (3 ml), added with diethylamine and stirred at 70° C. for 2.5 hours. Water was added and the mixture was extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure. The residue obtained was purified by silica gel column chromatography (chloroform:methanol=20:1) to give 71 mg of the title compound (38%).

Workup

  1. customthe mixture was reacted at 120° C. overnight
  2. extractionthe mixture was extracted with chloroform
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled away under reduced pressure
  6. customThe residue obtained
  7. customwas purified by silica gel column chromatography (methanol:chloroform=1:30)

Sources & evidence

ORD record
ord-7f98130b5fbf421abda3da464e7ee218
Source dataset
uspto-grants-1998_02
Patent number
US05719155

Reaction notes

Loading…