Tetrahydrofuran → HCID 23152992, compound

HRID 492730Notes

Reaction equation

HRID 492730 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[CH: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]C=CC=1)=O.CNCCC[N:41]1[CH2:46][CH2:45][N:44]([CH3:47])[CH2:43][CH2:42]1.[O:48]1CCCC1>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[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:19](=[O:48])[N:21]([CH3:24])[CH2:30][CH2:35][CH2:34][N:41]2[CH2:42][CH2:43][N:44]([CH3:47])[CH2:45][CH2:46]2)[CH:6]=1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 7219854N-methyl-3-(4-methylpiperazin-1-yl)propan-1-amine2×HCID 231531982-Amino-4-(2-fluoro-4-nitrophenoxy)pyridine

Product 1

HCID 23152992HCID 23152992, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(2-Fluoro-4-nitrophenoxy)pyridin-2-ylamine (200 mg) was dissolved in tetrahydrofuran (8 ml) under a nitrogen atmosphere, and then triethylamine (0.336 ml) and phenyl chloroformate (0.302 ml) were added dropwise thereto at room temperature, followed by stirring for 30 min. The reaction mixture was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (5 ml). N-methyl-N-[3-(4-methylpiperazin-1-yl)propyl]amine (0.300 ml) was added thereto, followed by stirring at room temperature overnight. N-methyl-N-[3-(4-methylpiperazin-1-yl)propyl]amine (0.200 ml) was further added thereto, followed by stirring at room temperature for 1 day. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of ammonium chloride. The organic layer was washed with a saturated aqueous solution of ammonium chloride, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:1). The solvent was evaporated under a reduced pressure to provide a crude product of 3-[4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl]-1-methyl-1-[3-(4-methylpiperazin-1-yl)propyl]urea. The crude product (357 mg) was dissolved in tetrahydrofuran (8 ml)-methanol (8 ml), and then 10% palladium carbon (170 mg) was added thereto under a nitrogen atmosphere, followed by replacing with hydrogen inside the system and stirring for 2 hrs. After replacing with nitrogen inside the system, the reaction mixture was filtered to remove the catalyst, which was washed with methanol. The filtrate was concentrated under a reduced pressure to give a residue, which was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:1, then ethyl acetate). Fractions containing the target compound were concentrated to give a residue, which was then suspended in diethyl ether-hexane (2:1). The solid was filtered and dried under aeration to provide the titled compound (91.0 mg, 27.3%) as pale yellow powder.

Workup

  1. customat room temperature
  2. concentrationThe reaction mixture was concentrated under a reduced pressure
  3. customto give a residue, which
  4. stirringby stirring at room temperature overnight
  5. stirringby stirring at room temperature for 1 day
  6. customThe reaction mixture was partitioned between ethyl acetate
  7. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride, water and brine in this order
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated under a reduced pressure
  10. customto give a residue, which
  11. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:1)
  12. customThe solvent was evaporated under a reduced pressure

Sources & evidence

ORD record
ord-9f6019e987bc4f62af69f1e2ad86d1bc
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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