Tetrahydrofuran → HCID 23153217, compound

HRID 492941Notes

Reaction equation

HRID 492941 reaction equation
[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH2:11])[CH:6]=1.[CH2:19]([N:21]([CH2:24]C)CC)C.ClC(O[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32]C=1)=O.CNC1CC[N:41]([CH:44]2[CH2:47][N:46]([CH3:48])[CH2:45]2)CC1.[O:49]1CCCC1>CCCCCC.CN(C)C=O>[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:19](=[O:49])[N:21]([CH3:24])[CH:34]2[CH2:33][CH2:32][N:41]([CH:44]3[CH2:45][N:46]([CH3:48])[CH2:47]3)[CH2:30][CH2:35]2)[CH:6]=1

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 231530124-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidineHCID 23153585HCID 23153585, compound

Product 1

HCID 23153217HCID 23153217, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

To a solution of 6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-ylamine (250 mg) in tetrahydrofuran (10 ml) were added triethylamine (0.307 ml) and phenyl chloroformate (0.264 ml) in this order, followed by stirring at room temperature for 30 min. The reaction mixture was concentrated to give a residue. To the residue was added N,N-dimethylformamide (5.0 ml), methyl-[1-(1-methylazetidin-3-yl)piperidin-4-yl]amine (1.07 g), followed by stirring at room temperature for 36 hrs. The reaction mixture was partitioned between ethyl acetate and an 1N aqueous solution of sodium hydroxide. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing a target compound were concentrated to give a powder, which was suspended hexane (5 ml). It was filtered off, dried under aeration to provide the titled compound (193 mg, 42.0%) as yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give a residue
  3. stirringby stirring at room temperature for 36 hrs
  4. customThe reaction mixture was partitioned between ethyl acetate
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationThe organic layer was concentrated
  9. customto give a residue, which
  10. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
  11. additionFractions containing a target compound
  12. concentrationwere concentrated
  13. customto give a powder, which
  14. filtrationIt was filtered off
  15. customdried under aeration

Sources & evidence

ORD record
ord-bdabd78e885948f48273a33d73885fc4
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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