Ethylene Glycol → 7-(5-chloro-2-fluorophenyl)-3-((2-methyl-1,3-dioxolan-2-yl)methoxy)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 335815Notes

Reaction equation

HRID 335815 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C:5]2([C:19]3[C:14](=[N:15][CH:16]=[C:17]([O:20][CH2:21][C:22](=[O:24])[CH3:23])[CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([C:25]2[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:26]=2[F:32])=[CH:10][CH:11]=3)[N:6]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:44](O)[CH2:45][OH:46].C([O-])(O)=O.[Na+]>S([O-])([O-])(=O)=O.[Cu+2].C1(C)C=CC=CC=1>[Cl:31][C:29]1[CH:28]=[CH:27][C:26]([F:32])=[C:25]([C:9]2[CH:8]=[C:7]3[C:5]4([CH2:4][O:3][C:2]([NH2:1])=[N:6]4)[C:19]4[C:14](=[N:15][CH:16]=[C:17]([O:20][CH2:21][C:22]5([CH3:23])[O:46][CH2:45][CH2:44][O:24]5)[CH:18]=4)[O:13][C:12]3=[CH:11][CH:10]=2)[CH:30]=1

Participants

7

Reactant 4

HCID 174Ethylene Glycol2×HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 673830551-(2'-amino-7-(5-chloro-2-fluorophenyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-3-yloxy)propan-2-one

Product 1

HCID 584662537-(5-chloro-2-fluorophenyl)-3-((2-methyl-1,3-dioxolan-2-yl)methoxy)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 1140TolueneSolvent

Procedure

To a vial charged with 1-(2′-amino-7-(5-chloro-2-fluorophenyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-3-yloxy)propan-2-one (0.140 g, 0.308 mmol), p-toluenesulfonic acid (0.159 g, 0.925 mmol), and 4 Angstrom molecular seives was added 3 mL toluene. The resulting mixture was treated with ethylene glycol (0.022 mL, 0.401 mmol) and was heated to reflux. After stirring for 10 hours, copper(ii) sulfate (0.059 g, 0.617 mmol) was added followed by an additional portion of ethylene glycol (0.022 mL, 0.401 mmol). The reaction mixture was heated to reflux for an additional 4 hours before being allowed to cool to RT. The mixture was poured into saturated NaHCO3 (25 mL) solution and extracted with EtOAc (3×25 mL). The organics were washed with brine, dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography gave 7-(5-chloro-2-fluorophenyl)-3-((2-methyl-1,3-dioxolan-2-yl)methoxy)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine. MS m/z=498.0 [M+H].

Workup

  1. temperaturewas heated to reflux
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for an additional 4 hours
  4. extractionextracted with EtOAc (3×25 mL)
  5. washThe organics were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customPurification of the crude residue by column chromatography

Sources & evidence

ORD record
ord-ef8ce861e0ee4b71899812c8e76d1ad9
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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