Triphenylphosphine → 6-(3-(2,4-Difluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1930005Notes

Reaction equation

HRID 1930005 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([CH:23]([CH3:25])[CH3:24])=[N:21][N:22]=3)[N:19]=2)=[CH:12][NH:11][N:10]=1.[O:26]1[CH2:31][CH2:30][CH:29](O)[CH2:28][CH2:27]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([CH:23]([CH3:25])[CH3:24])=[N:21][N:22]=3)[N:19]=2)=[CH:12][N:11]([CH:29]2[CH2:30][CH2:31][O:26][CH2:27][CH2:28]2)[N:10]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 74956Tetrahydro-4H-pyran-4-olHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 178440301HCID 178440301, compound

Product 1

HCID 579299506-(3-(2,4-Difluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazineYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The 6-(3-(2,4-difluorophenyl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (0.30 g, 0.88 mmol) in THF (4 mL) was treated with tetrahydro-2H-pyran-4-ol (0.12 g, 1.1 mmol; Example #L.1.1) and Ph3P (0.35 g, 1.3 mmol). Diethyl azodicarboxylate (40 wt % in toluene, 0.52 mL, 1.32 mmol; TCI) was then added and the mixture stirred at ambient temperature for about 1 h. The reaction was concentrated under reduced pressure and then purified by silica gel chromatography using EtOAc/MeOH (stepwise gradient, 95:5 then 9:1) to isolate lower Rf major product with impurities. The material was purified further by RP-HPLC (Table 1, Method d). Concentration of the desired fractions under reduced pressure resulted in a solid that was collected by filtration and then dried to give the title compound (0.063 g, 17%) as a white solid: LC/MS (Table 1, Method a) Rt=2.40 min; MS m/z: 425.2 (M+H)+.

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. custompurified by silica gel chromatography
  3. custom9:1) to isolate lower Rf major product with impurities
  4. customThe material was purified further by RP-HPLC (Table 1, Method d)
  5. customConcentration of the desired fractions under reduced pressure resulted in a solid
  6. filtrationthat was collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-32c42d6d68dd40da883716ee27d763e4
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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