N,N,N',N'-Tetramethylazodicarboxamide → 2-[3-(4-Morpholinyl)phenoxy]ethyl 3-(1-piperazinyl)-2-pyrazinyl ether

HRID 493289Notes

Reaction equation

HRID 493289 reaction equation
N(C(N(C)C)=O)=NC(N(C)C)=O.C(OC([N:20]1[CH2:25][CH2:24][N:23]([C:26]2[C:27]([O:32][CH2:33][CH2:34][OH:35])=[N:28][CH:29]=[CH:30][N:31]=2)[CH2:22][CH2:21]1)=O)(C)(C)C.[N:36]1([C:42]2[CH:43]=[C:44](O)[CH:45]=[CH:46][CH:47]=2)[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[N:23]1([C:26]2[C:27]([O:32][CH2:33][CH2:34][O:35][C:46]3[CH:45]=[CH:44][CH:43]=[C:42]([N:36]4[CH2:37][CH2:38][O:39][CH2:40][CH2:41]4)[CH:47]=3)=[N:28][CH:29]=[CH:30][N:31]=2)[CH2:22][CH2:21][NH:20][CH2:25][CH2:24]1

Participants

6

Reactant 4

HCID 4278N,N,N',N'-TetramethylazodicarboxamideHCID 11776TriphenylphosphineHCID 1413433-MorpholinophenolHCID 114160742-[3-(4-Tert-butoxycarbonyl-1-piperazinyl)-2-pyrazinyloxy]ethanol

Product 1

HCID 220362362-[3-(4-Morpholinyl)phenoxy]ethyl 3-(1-piperazinyl)-2-pyrazinyl etherYield 10.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1′-Azobis(N,N-dimethylformamide) (TMAD; 256 mg, 1.50 mmol) was added to a solution of 2-[3-(4-tert-butoxycarbonyl-1-piperazinyl)-2-pyrazinyloxy]ethanol (400 mg. 1.24 mmol; prepared in Example 52, Step 2), 3-(4-morpholinyl)phenol (441 mg, 1 23 mmol) and triphenylphosphine (646 mg, 2.46 mmol) in THF (3 mL). The reaction mixture was stirred at room temperature for 2.5 h and then concentrated. The residue was purified by repeated chromatography on silica gel using toluene and toluene/EtOAc (8.2) as eluents Solvents were evaporated and the residue was treated with CH2Cl2/TFA/H2O (1:0.9:0. 1; 5 mL) at room temperature for 0.5 h. After concentration. 5 M NaOH was added followed by extraction with CH2Cl2. The organic phase was dried (K2CO3), filtered, and concentrated The residue was purified by chromatography on silica gel using CHCl3/MeOH (9 1) as eluent to give 50 mg (10%) of the title product as on oil. HRMS m/z calcd for C20H27N5O3 (M)+ 385.2114, found 385 2100.

Workup

  1. concentrationconcentrated
  2. customThe residue was purified
  3. customwere evaporated
  4. additionthe residue was treated with CH2Cl2/TFA/H2O (1:0.9:0. 1; 5 mL) at room temperature for 0.5 h
  5. concentrationAfter concentration
  6. addition5 M NaOH was added
  7. extractionfollowed by extraction with CH2Cl2
  8. dry with materialThe organic phase was dried (K2CO3)
  9. filtrationfiltered
  10. concentrationconcentrated The residue
  11. customwas purified by chromatography on silica gel

Sources & evidence

ORD record
ord-59dba8887de44d9a9df8053040adde7f
Source dataset
uspto-grants-2009_05
Patent number
US07534794B2

Reaction notes

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