Diethyl Ether → HCID 23153063, compound

HRID 492815Notes

Reaction equation

HRID 492815 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][C:3]=1[Cl:24].C(N(CC)CC)C.[F:32][P-](F)(F)(F)(F)F.[N:39]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=2N=N1.C([O:61][CH2:62][CH3:63])C.CN(C)[CH:66]=[O:67]>CCCCCC>[Cl:24][C:3]1[CH:4]=[C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])[CH:8]=2)[CH:22]=[CH:23][C:2]=1[NH:1][C:62](=[O:61])[CH2:63][C:66]([NH:39][C:43]1[CH:44]=[CH:45][C:46]([F:32])=[CH:47][CH:42]=1)=[O:67]

Participants

7

Reactant 5

HCID 3283Diethyl EtherHCID 6228DimethylformamideHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 57677479HCID 57677479, compound

Product 1

HCID 23153063HCID 23153063, compoundYield 81.3%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

Piperidine-1-carboxylic acid [4-(4-amino-3-chlorophenoxy)pyridin-2-yl]amide (100 mg) was dissolved in N,N-dimethylformamide (2 ml) under a nitrogen atmosphere, and then N-(4-fluorophenyl)malonic acid (171 mg), triethylamine (0.121 ml) and (1H-1,2,3-benzotriazol-1-yloxy)[tri(dimethylamino)]phosphonium hexafluorophosphate (383 mg) were added thereto at 50° C., followed by stirring at the same temperature for 1 hr and 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, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:ethanol=49:1). Fractions containing a crude product were concentrated to give a residue, which was then further purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:ethanol=49:1). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (5 ml)-hexane (5 ml) was added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (123 mg, 81.3%) as white powder.

Workup

  1. customat 50° C.
  2. custompartitioned between ethyl acetate
  3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. customto give a residue, which
  7. customwas purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:ethanol=49:1)
  8. additionFractions containing a crude product
  9. concentrationwere concentrated
  10. customto give a residue, which
  11. customwas then further purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:ethanol=49:1)
  12. additionFractions containing the target compound
  13. concentrationwere concentrated
  14. customto give a residue
  15. filtrationThe solid was filtered off
  16. customdried under aeration

Sources & evidence

ORD record
ord-0560cb349b7245c281dad2a17ed4d6d3
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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