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 335815노트

반응식

HRID 335815 반응식
[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

참가 물질

7

반응물 4

HCID 174Ethylene Glycol2회HCID 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

생성물 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

시약·촉매·용매 2

HCID 24462Copper Sulfate촉매HCID 1140Toluene용매

실험 절차

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].

후처리

  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

출처 및 근거

ORD 기록
ord-ef8ce861e0ee4b71899812c8e76d1ad9
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883782B2

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