Triethylamine → [1,4']Bipiperidinyl-1'-carboxylic acid [6-(4-nitro-2-fluorophenoxy)pyrimidin-4-yl]amide

HRID 492728Notes

Reaction equation

HRID 492728 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=2[F:18])[N:5]=[CH:4][N:3]=1.C(N(CC)CC)C.Cl[C:27](OC1C=CC=CC=1)=[O:28].[N:36]1([CH:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1>O1CCCC1.CN(C)C=O>[N+:15]([C:12]1[CH:13]=[CH:14][C:9]([O:8][C:6]2[N:5]=[CH:4][N:3]=[C:2]([NH:1][C:27]([N:45]3[CH2:46][CH2:47][CH:42]([N:36]4[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]4)[CH2:43][CH2:44]3)=[O:28])[CH:7]=2)=[C:10]([F:18])[CH:11]=1)([O-:17])=[O:16]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 786071,4'-BipiperidineHCID 231530124-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine

Product 1

HCID 57677652[1,4']Bipiperidinyl-1'-carboxylic acid [6-(4-nitro-2-fluorophenoxy)pyrimidin-4-yl]amideYield 61.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine (40 mg) was dissolved in tetrahydrofuran (2 ml) under a nitrogen atmosphere, and then triethylamine (0.045 ml) and phenyl chloroformate (0.040 ml) were added dropwise thereto, followed by stirring at room temperature for 1 hr. The reaction mixture was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (2 ml). 4-(Piperidin-1-yl)piperidine (108 mg) was added thereto, followed by stirring for 10 min. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of ammonium chloride. The organic layer was washed with a saturated aqueous solution of ammonium chloride, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:1 to 1:2). Fractions containing the target compound were concentrated under a reduced pressure, and dried in vacuum to provide the titled compound (43.9 mg, 61.7%) as a yellow solid.

Workup

  1. concentrationThe reaction mixture was concentrated under a reduced pressure
  2. customto give a residue, which
  3. stirringby stirring for 10 min
  4. customThe reaction mixture was partitioned between ethyl acetate
  5. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride, water and brine in this order
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under a reduced pressure
  8. customto give a residue, which
  9. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:1 to 1:2)
  10. additionFractions containing the target compound
  11. concentrationwere concentrated under a reduced pressure
  12. customdried in vacuum

Sources & evidence

ORD record
ord-032a7b2f41564a16be680411775badef
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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