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 335815ノート

反応式

HRID 335815 の反応式
[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

参加物

7

反応物 4

HCID 174Ethylene Glycol2 回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

生成物 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

試薬・触媒・溶媒 2

HCID 24462Copper Sulfate触媒HCID 1140Toluene溶媒

実験手順

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].

後処理

  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

出典と根拠

ORDレコード
ord-ef8ce861e0ee4b71899812c8e76d1ad9
出典データセット
uspto-grants-2014_11
特許番号
US08883782B2

反応ノート

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