Diethyl Ether → N-(4-Fluorophenyl)-N'-(4-{2-[(pyrrolidine-1-carbonyl)amino]pyridin-4-yloxy}phenyl)malonamide

HRID 492818Notes

Reaction equation

HRID 492818 reaction equation
[NH2:1][C:2]1[CH:22]=[CH:21][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:30][P-](F)(F)(F)(F)F.[N:37]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2N=N1.C([O:59][CH2:60][CH3:61])C.CN(C)[CH:64]=[O:65]>CCCCCC>[F:30][C:44]1[CH:43]=[CH:42][C:41]([NH:37][C:60](=[O:59])[CH2:61][C:64]([NH:1][C:2]2[CH:22]=[CH:21][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]4[CH2:20][CH2:19][CH2:18][CH2:17]4)=[O:15])[CH:8]=3)=[CH:4][CH:3]=2)=[O:65])=[CH:40][CH:45]=1

Participants

7

Reactant 5

HCID 3283Diethyl EtherHCID 6228DimethylformamideHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 231532634-(4-Aminophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine

Product 1

HCID 23153583N-(4-Fluorophenyl)-N'-(4-{2-[(pyrrolidine-1-carbonyl)amino]pyridin-4-yloxy}phenyl)malonamideYield 83.4%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

4-(4-Aminophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine (30 mg) was dissolved in N,N-dimethylformamide (1 ml) under a nitrogen atmosphere, and then N-(4-fluorophenyl)malonic acid (59.5 mg), triethylamine (0.042 ml) and (1H-1,2,3-benzotriazol-1-yloxy)[tri(dimethylamino)]phosphonium hexafluorophosphate (134 mg) were added thereto at 50° C., followed by stirring at the same temperature for 30 min. 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 (eluent; hexane:ethyl acetate=1:5, then ethyl acetate). 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 (40.4 mg, 83.4%) as a pale brown 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 (eluent
  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-bc6833bc1a6c4982a978e9e16e6dbebc
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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