Hexane → HCID 23153262, compound

HRID 492825Notes

Reaction equation

HRID 492825 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:28])[CH2:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[O:19])=[C:11]([F:29])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH2:30]([N:32]([CH2:35][CH3:36])[CH2:33]C)[CH3:31].ClC(OC1C=CC=CC=1)=[O:39].CCCCCC>O1CCCC1.C(O)C.C(OCC)C>[F:29][C:11]1[CH:10]=[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:33]([N:32]3[CH2:35][CH2:36][CH2:31][CH2:30]3)=[O:39])[CH:7]=2)[CH:14]=[CH:13][C:12]=1[NH:15][C:16](=[O:28])[CH2:17][C:18]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)=[O:19]

Participants

8

Reactant 4

HCID 8058HexaneHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 23152971HCID 23152971, compound

Product 1

HCID 23153262HCID 23153262, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 702EthanolCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]-N′-(4-fluorophenyl)malonamide (30 mg) in tetrahydrofuran (2.4 ml) was added triethylamine (0.021 ml), and then phenyl chloroformate (0.0189 ml) was added dropwise thereto while cooling in an ice water bath, followed by stirring for 20 min. The reaction mixture was concentrated under a reduced pressure. To a suspension of the residue in N,N-dimethylformamide (1.2 ml) was added pyrrolidine (0.0251 ml) while cooling in an ice water bath, followed by raising the temperature to room temperature and stirring for 1 hr. The reaction mixture was partitioned between ethyl acetate (50 ml) and a 1 N aqueous solution of sodium hydroxide (30 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=10:1). Fractions containing the target compound were concentrated to give a residue, which was then further subjected to silica gel filtration (FUJI Silysia NH). The filtrate was concentrated under a reduced pressure to give a residue, to which hexane (3 ml), diethyl ether (1 ml) and ethanol (1 drop) were added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (12.3 mg, 33.0%) as pale red powder.

Workup

  1. temperaturewhile cooling in an ice water bath
  2. concentrationThe reaction mixture was concentrated under a reduced pressure
  3. additionTo a suspension of the residue in N,N-dimethylformamide (1.2 ml)
  4. additionwas added pyrrolidine (0.0251 ml)
  5. temperaturewhile cooling in an ice water bath
  6. stirringstirring for 1 hr
  7. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  8. washThe organic layer was washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customThe solvent was evaporated
  11. customto give a residue, which
  12. customwas then purified by silica gel column chromatography (eluent
  13. additionFractions containing the target compound
  14. concentrationwere concentrated
  15. customto give a residue, which
  16. filtrationwas then further subjected to silica gel filtration (FUJI Silysia NH)
  17. concentrationThe filtrate was concentrated under a reduced pressure
  18. customto give a residue
  19. filtrationThe solid was filtered off
  20. customdried under aeration

Sources & evidence

ORD record
ord-cd71b470bf904ab18165c589aa401024
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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