Diethyl Ether → HCID 23153024, compound

HRID 492819Notes

Reaction equation

HRID 492819 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:28][P-](F)(F)(F)(F)F.[N:35]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2N=N1.C([O:57][CH2:58][CH3:59])C.CN(C)[CH:62]=[O:63]>CCCCCC>[CH3:17][N:16]([CH3:18])[C:14](=[O:15])[NH:13][C:9]1[CH:8]=[C:7]([O:6][C:5]2[CH:19]=[CH:20][C:2]([NH:1][C:58](=[O:57])[CH2:59][C:62]([NH:35][C:39]3[CH:40]=[CH:41][C:42]([F:28])=[CH:43][CH:38]=3)=[O:63])=[CH:3][CH:4]=2)[CH:12]=[CH:11][N:10]=1

Participants

7

Reactant 5

HCID 3283Diethyl EtherHCID 6228DimethylformamideHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 23153281HCID 23153281, compound

Product 1

HCID 23153024HCID 23153024, compoundYield 87.4%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

1-[4-(4-Aminophenoxy)pyridin-2-yl]-3,3dimethylurea (30 mg) was dissolved in N,N-dimethylformamide (1 ml) under a nitrogen atmosphere, and then N-(4-fluorophenyl)malonic acid (65.1 mg), triethylamine (0.046 ml) and (1H-1,2,3-benzotriazol-1-yloxy)[tri(dimethylamino)]phosphonium hexafluorophosphate (146 mg) were added thereto at 50° C., followed by stirring at the same temperature for 1.5 hr. The reaction mixture was cooled down to room temperature, and partitioned between ethyl acetate and a 1 N aqueous solution of sodium hydroxide. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, a saturated aqueous solution of ammonium chloride, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; hexane:ethyl acetate=1:5 to 1:8). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (2 ml)-hexane (2 ml) was added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (43.4 mg, 87.4%) as a white solid.

Workup

  1. customat 50° C.
  2. custompartitioned between ethyl acetate
  3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate
  4. dry with materiala saturated aqueous solution of ammonium chloride, water and brine in this order, and dried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. customto give a residue, which
  7. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent; hexane:ethyl acetate=1:5 to 1:8)
  8. additionFractions containing the target compound
  9. concentrationwere concentrated
  10. customto give a residue
  11. filtrationThe solid was filtered off
  12. customdried under aeration

Sources & evidence

ORD record
ord-c1d6c0c0b2314cd1ac2f31b91b3388b7
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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