Triphenylphosphine → 1-(cyclopropylmethyl)-5-[3-(1-methyl-1H-benzimidazol-2-yl)propoxy]-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 333732Notes

Reaction equation

HRID 333732 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:36]1([CH2:39][N:40]2[CH:45]=[C:44]([OH:46])[C:43](=[O:47])[C:42]([C:48]3[N:52]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[N:51]=[CH:50][CH:49]=3)=[N:41]2)[CH2:38][CH2:37]1.[CH3:59][N:60]1[C:64]2[CH:65]=[CH:66][CH:67]=[CH:68][C:63]=2[N:62]=[C:61]1[CH2:69][CH2:70][CH2:71]O>C1(C)C=CC=CC=1>[CH:36]1([CH2:39][N:40]2[CH:45]=[C:44]([O:46][CH2:71][CH2:70][CH2:69][C:61]3[N:60]([CH3:59])[C:64]4[CH:65]=[CH:66][CH:67]=[CH:68][C:63]=4[N:62]=3)[C:43](=[O:47])[C:42]([C:48]3[N:52]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[N:51]=[CH:50][CH:49]=3)=[N:41]2)[CH2:37][CH2:38]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 45852153-(1-Methyl-1H-benzimidazol-2-yl)propan-1-olHCID 895865391-(cyclopropylmethyl)-5-hydroxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 566541301-(cyclopropylmethyl)-5-[3-(1-methyl-1H-benzimidazol-2-yl)propoxy]-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 45.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Toluene (10 mL) was added to di-tert-butyl diazene-1,2-dicarboxylate (173 mg) and triphenylphosphine (229 mg) and the mixture was stirred at room temperature for 10 min. Then, 1-(cyclopropylmethyl)-5-hydroxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (154 mg), and further, 3-(1-methyl-1H-benzimidazol-2-yl)propan-1-ol (143 mg) were added, and the mixture was stirred at room temperature for 22 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol). A fraction containing the title compound was again purified by NH silica gel column chromatography (hexane/ethyl acetate), and crystallized from hexane/ethyl acetate to give the title compound (110 mg) as white prisms.

Workup

  1. stirringthe mixture was stirred at room temperature for 22 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe residue was purified by silica gel column chromatography (ethyl acetate/methanol)
  4. additionA fraction containing the title compound
  5. customwas again purified by NH silica gel column chromatography (hexane/ethyl acetate)
  6. customcrystallized from hexane/ethyl acetate

Sources & evidence

ORD record
ord-d511b638bb79418dbfdab04623616047
Source dataset
uspto-grants-2014_11
Patent number
US08883788B2

Reaction notes

Loading…