Tributylphosphine → N-cyclopropyl-1-{4-[(ethylamino)carbonyl]phenyl}-5-{3-[4-(trifluoromethoxy)phenoxy]propyl}-1H-1,2,3-triazole-4-carboxamide

HRID 1717404Notes

Reaction equation

HRID 1717404 reaction equation
[F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.C(P(CCCC)CCCC)CCC.[CH:26]1([NH:29][C:30]([C:32]2[N:33]=[N:34][N:35]([C:41]3[CH:46]=[CH:45][C:44]([C:47]([NH:49][CH2:50][CH3:51])=[O:48])=[CH:43][CH:42]=3)[C:36]=2[CH2:37][CH2:38][CH2:39]O)=[O:31])[CH2:28][CH2:27]1.N(/C(N1CCCCC1)=O)=N\C(N1CCCCC1)=O>C1(C)C=CC=CC=1>[CH:26]1([NH:29][C:30]([C:32]2[N:33]=[N:34][N:35]([C:41]3[CH:42]=[CH:43][C:44]([C:47]([NH:49][CH2:50][CH3:51])=[O:48])=[CH:45][CH:46]=3)[C:36]=2[CH2:37][CH2:38][CH2:39][O:10][C:7]2[CH:6]=[CH:5][C:4]([O:3][C:2]([F:11])([F:12])[F:1])=[CH:9][CH:8]=2)=[O:31])[CH2:27][CH2:28]1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 70015p-(Trifluoromethoxy)phenolHCID 5702657diazenedicarboxylic acid bis(N,N-piperidide)HCID 57665173HCID 57665173, compound

Product 1

HCID 57664933N-cyclopropyl-1-{4-[(ethylamino)carbonyl]phenyl}-5-{3-[4-(trifluoromethoxy)phenoxy]propyl}-1H-1,2,3-triazole-4-carboxamideYield 64.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent4×

Procedure

To a solution of 4-(trifluoromethoxy)phenol (52 mg) in toluene (0.5 ml) was added a solution of tributylphosphine (51 mg) in toluene (0.5 ml) under stirring, a solution of N-cyclopropyl-1-{4-[(ethylamino)carbonyl]phenyl}-5-(3-hydroxypropyl)-1H-1,2,3-triazole-4-carboxamide (29 mg) in toluene (0.5 ml) and a solution of 1,1′-[(E)-diazene-1,2-diyldicarbonyl]dipiperidine in toluene (0.5 ml) were successively added, and the mixture was stirred at room temperature for 64 hr. The reaction mixture was filtered through a filter tube (Biospin column, Bio-Rad), and washed with 1 ml of ethyl acetate. The filtrates were combined, 1 ml of ethyl acetate and 1 ml of saturated aqueous sodium hydrogen carbonate solution were added, and the mixture was vigorously stirred at room temperature for 30 min. The organic layer was recovered using Presep™ Dehydration (Wako Pure Chemical Industries, Ltd.) and concentrated to dryness. The residue was dissolved in DMSO (0.7 ml) and purified by preparative HPLC (Gilson, Inc., high-throughput purification system, column: YMC CombiPrep ODS-A S-5 μm, 50×20 mm, solvent: solution A; 0.1% formic acid aqueous solution, solution B; 0.1% formic acid acetonitrile solution, gradient cycle: 0 min (solution A/solution B=95/5), 1.00 min (solution A/solution B=95/5), 5.20 min (solution A/solution B=5/95), 6.40 min (solution A/solution B=5/95), 6.50 min (solution A/solution B=95/5), 6.60 min (solution A/solution B=95/5), flow rate: 25 ml/min, detection method: UV 220 nm) to give the title compound (27 mg) (LC/MS purity 100%, ESI+:518 [M+H]+).

Workup

  1. stirringthe mixture was stirred at room temperature for 64 hr
  2. filtrationThe reaction mixture was filtered through a filter tube (Biospin column, Bio-Rad)
  3. washwashed with 1 ml of ethyl acetate
  4. addition1 ml of ethyl acetate and 1 ml of saturated aqueous sodium hydrogen carbonate solution were added
  5. stirringthe mixture was vigorously stirred at room temperature for 30 min
  6. customThe organic layer was recovered
  7. concentrationconcentrated to dryness
  8. dissolutionThe residue was dissolved in DMSO (0.7 ml)
  9. custompurified by preparative HPLC (Gilson, Inc., high-throughput purification system, column: YMC CombiPrep ODS-A S-5 μm, 50×20 mm, solvent: solution A; 0.1% formic acid aqueous solution, solution B; 0.1% formic acid acetonitrile solution, gradient cycle: 0 min (solution A/solution B=95/5), 1.00 min (solution A/solution B=95/5), 5.20 min (solution A/solution B=5/95), 6.40 min (solution A/solution B=5/95), 6.50 min (solution A/solution B=95/5), 6.60 min (solution A/solution B=95/5), flow rate: 25 ml/min, detection method: UV 220 nm)

Sources & evidence

ORD record
ord-a5b5fc9c3bdc4b5290db8172c28b6c7a
Source dataset
uspto-grants-2010_09
Patent number
US07803822B2

Reaction notes

Loading…