3,4-dihydro-2H-pyran → HCID 66855410, compound

HRID 1529999Notes

Reaction equation

HRID 1529999 reaction equation
[C:1]1([C:7]2[N:8]=[C:9]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24](=[O:26])[CH3:25])[CH:18]=3)[S:10][C:11]=2[C:12]2[NH:16][CH:15]=[N:14][N:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:39]1[CH:44]=[CH:43][CH2:42][CH2:41][CH2:40]1>O1CCCC1.C(OCC)(=O)C>[C:1]1([C:7]2[N:8]=[C:9]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24](=[O:26])[CH3:25])[CH:18]=3)[S:10][C:11]=2[C:12]2[N:16]=[CH:15][N:14]([CH:40]3[CH2:41][CH2:42][CH2:43][CH2:44][O:39]3)[N:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178474048HCID 178474048, compound

Product 1

HCID 66855410HCID 66855410, compoundYield 88.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-{4-[4-phenyl-5-(4H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamide (65 mg, 0.18 mmol) produced in Example 1-B (vi) in tetrahydrofuran (3.0 mL) were added p-toluenesulfonic acid monohydrate (41 mg, 0.22 mmol) and 3,4-dihydro-2H-pyran (140 mg, 1.7 mmol), and the mixture was heated under reflux for 3 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (40 mL), and washed with saturated aqueous sodium bicarbonate solution (30 mL). The aqueous layer was extracted with ethyl acetate (40 mL), the combined organic layer was dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→100/0) to give the title compound (71.0 mg, 88%) as a white solid.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 3 hr
  3. washwashed with saturated aqueous sodium bicarbonate solution (30 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (40 mL)
  5. dry with materialthe combined organic layer was dried over anhydrous magnesium sulfate
  6. filtrationthe insoluble material was filtered off
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→100/0)

Sources & evidence

ORD record
ord-fc093c7b7191487687ebc46d2f61203f
Source dataset
uspto-grants-2015_07
Patent number
US09090601B2

Reaction notes

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