Phenyl chloroformate → 4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-nitrophenoxy)pyridin-2-yl]amide

HRID 492992Notes

Reaction equation

HRID 492992 reaction equation
[N+:1]([C:4]1[CH:17]=[CH:16][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH2:15])[CH:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl[C:19](OC1C=CC=CC=1)=[O:20].Cl.Cl.Cl.[N:31]1([CH2:35][CH2:36][N:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH2:34][CH2:33][CH2:32]1>O1CCCC1.CO.C(N(CC)CC)C>[N+:1]([C:4]1[CH:17]=[CH:16][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:19]([N:40]3[CH2:39][CH2:38][N:37]([CH2:36][CH2:35][N:31]4[CH2:32][CH2:33][CH2:34]4)[CH2:42][CH2:41]3)=[O:20])[CH:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

7

Reactant 3

HCID 15891Phenyl chloroformateHCID 229367164-(4-Nitrophenoxy)pyridin-2-amineHCID 231529971-[2-(Azetidin-1-yl)ethyl]piperazine trihydrochloride

Product 1

HCID 576776864-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-nitrophenoxy)pyridin-2-yl]amide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Procedure

4-(4-Nitrophenoxy)pyridin-2-ylamine (60 mg) was dissolved in tetrahydrofuran (3 ml) under a nitrogen atmosphere. Triethylamine (0.109 ml) and phenyl chloroformate (0.0975 ml) were added thereto while cooling in an ice water bath, followed by warming to room temperature and stirring for 30 min. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (30 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml), water (30 ml), brine (30 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, to which was then added N-dimethylformamide (3 ml). And then an 1.0 M solution of 1-[2-(azetidin-1-yl)ethyl]piperazine trihydrochloride in methanol (0.884 ml) and triethylamine (0.261 ml) were added thereto, followed by stirring for 4 hrs. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of ammonium chloride (30 ml). The organic layer was washed with a saturated aqueous solution of ammonium chloride (30 ml), water (30 ml), and brine (30 ml), 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, ethyl acetate, then ethyl acetate:methanol=9:1). Fractions containing the target compound were concentrated to provide a crude product of the titled compound (122 mg) as a pale yellow solid.

Workup

  1. temperaturewhile cooling in an ice water bath
  2. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml), water (30 ml), brine (30 ml) in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. customto give a residue
  7. stirringby stirring for 4 hrs
  8. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  9. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride (30 ml), water (30 ml), and brine (30 ml)
  10. dry with materialdried over anhydrous sodium sulfate
  11. customThe solvent was evaporated
  12. customto give a residue, which
  13. customwas then purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate
  14. additionFractions containing the target compound
  15. concentrationwere concentrated

Sources & evidence

ORD record
ord-14bcfc93ecbb4aa9a2d5c5cca8acdd3e
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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