Diethyl Ether → HCID 57677567, compound

HRID 492813Notes

Reaction equation

HRID 492813 reaction equation
[NH2:1][C:2]1[CH:28]=[CH:27][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][CH:19]([N:22]4[CH2:26][CH2:25][CH2:24][CH2:23]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][C:3]=1[Cl:29].C(N(CC)CC)C.[F:37][P-](F)(F)(F)(F)F.[N:44]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=2N=N1.C([O:66][CH2:67][CH3:68])C.CN(C)[CH:71]=[O:72]>>[F:37][C:51]1[CH:50]=[CH:49][C:48]([NH:44][C:67](=[O:66])[CH2:68][C:71]([NH:1][C:2]2[CH:28]=[CH:27][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]4[CH2:21][CH2:20][CH:19]([N:22]5[CH2:26][CH2:25][CH2:24][CH2:23]5)[CH2:18][CH2:17]4)=[O:15])[CH:8]=3)=[CH:4][C:3]=2[Cl:29])=[O:72])=[CH:47][CH:52]=1

Participants

6

Reactant 5

HCID 3283Diethyl EtherHCID 6228DimethylformamideHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 23153500HCID 23153500, compound

Product 1

HCID 57677567HCID 57677567, compoundYield 35.1%

Procedure

4-(Pyrrolidin-1-yl)piperidine-1-carboxylic acid [4-(4-amino-3-chlorophenoxy)pyridin-2-yl]amide (129 mg) was dissolved in N,N-dimethylformamide (2 ml) under a nitrogen atmosphere, and then N-(4-fluorophenyl)malonic acid (183 mg), triethylamine (0.130 ml) and (1H-1,2,3-benzotriazol-1-yloxy)[tri(dimethylamino)]phosphonium hexafluorophosphate (411 mg) were added thereto at 50° C., followed by stirring at the same temperature for 5 hrs and 30 min. The reaction mixture was cooled down to room temperature, followed by stirring for 2 days. The reaction mixture was 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 then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:ethanol=19:1). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether was added to precipitate crystals. The crystals were filtered off and dried under aeration to provide the titled compound (64.7 mg, 35.1%) as white crystals.

Workup

  1. customat 50° C.
  2. stirringby stirring for 2 days
  3. customThe reaction mixture was partitioned between ethyl acetate
  4. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated
  7. customto give a residue, which
  8. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:ethanol=19:1)
  9. additionFractions containing the target compound
  10. concentrationwere concentrated
  11. customto give a residue
  12. customto precipitate crystals
  13. filtrationThe crystals were filtered off
  14. customdried under aeration

Sources & evidence

ORD record
ord-c17b7bb8038142c7ae815416d9af3489
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

Loading…