Hydrochloric Acid → 6-((6-Phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)isoquinoline hydrochloride

HRID 40296Notes

Reaction equation

HRID 40296 reaction equation
COC1C=C2C(C(NCC3N4N=[C:21]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH:22]=[N:23][C:18]4=NN=3)=CC=N2)=NC=1.CN1C[C:38]2[C:33](=[CH:34][CH:35]=[C:36]([C:40]3[CH:41]=[CH:42][C:43]4[N:44]([C:46]([CH2:49]NC(=O)OC(C)(C)C)=[N:47][N:48]=4)[N:45]=3)[CH:37]=2)C1=O.[ClH:59]>>[ClH:59].[C:36]1([C:40]2[CH:41]=[CH:42][C:43]3[N:44]([C:46]([CH2:49][C:26]4[CH:25]=[C:24]5[C:29](=[CH:28][CH:27]=4)[CH:18]=[N:23][CH:22]=[CH:21]5)=[N:47][N:48]=3)[N:45]=2)[CH:35]=[CH:34][CH:33]=[CH:38][CH:37]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 57691219Tert-butyl (6-(2-methyl-1-oxoisoindolin-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamateHCID 576912317-methoxy-N-((6-phenyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-yl)methyl)-1,5-naphthyridin-4-amine

Product 1

HCID 675031546-((6-Phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)isoquinoline hydrochloride

Procedure

A 10 mL, CEM microwave vessel was charged with 3 (0.1040 g, 0.427 mmol), 1-(5-phenylpyridin-2-yl)hydrazine (4, 0.119 g, 0.641 mmol), a stirbar and 1 mL concentrated HCl. The vessel was sealed, and fitted with an 18-gauge needle and an Argon inlet. The slurry was placed in a heating block at 115° C. for 15 minutes with stirring. A volatile substance evolved during this time. The vessel was briefly cooled, and the seal was replaced. The vessel was irradiated on a CEM Explorer using the following parameters: ramp time 20 s, hold time 10 min, hold temperature 150° C., powermax=on, 75 W max. The resultant turbid aqueous solution was filtered and concentrated in vacuo. The solids were suspended in 3 mL hot EtOH, and cooled. The precipitate was isolated by filtration and washed with EtOH (3×3 mL). The solids were taken up in 2 mL H2O, and filtered through a 0.1 μm PVDF Ultra-free-CL centrifugal filter (Millipore Corp, PN UFC40W00, 2000 g for 5 minutes). The aqueous filtrate was lyophilized to afford 6-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)isoquinoline hydrochloride. Anal. Calcd for C21H15N5.HCl.1.7 H2O: C, 62.36; H, 4.83; N, 17.31. Found: C, 62.39±0.08; H, 4.48±0.02; N, 17.28±0.03.

Workup

  1. customThe vessel was sealed
  2. customfitted with an 18-gauge needle and an Argon inlet
  3. temperatureThe vessel was briefly cooled
  4. customThe vessel was irradiated on a CEM Explorer
  5. customtime 20 s
  6. customtime 10 min
  7. customtemperature 150° C., powermax=
  8. filtrationwas filtered
  9. concentrationconcentrated in vacuo
  10. temperaturecooled
  11. customThe precipitate was isolated by filtration
  12. washwashed with EtOH (3×3 mL)
  13. filtrationfiltered through a 0.1 μm PVDF Ultra-free-CL centrifugal
  14. filtrationfilter (Millipore Corp, PN UFC40W00, 2000 g for 5 minutes)

Sources & evidence

ORD record
ord-d96b594d46764bb8a99b39e3f61fb613
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Reaction notes

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