Carbon Dioxide → 6-(1-(6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline

HRID 219258Notes

Reaction equation

HRID 219258 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([NH:8][NH:9][C:10](=O)[CH:11]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[CH:18][CH:17]=[CH:16]3)[CH3:12])=[CH:4][CH:3]=1.C(O)C.C(=O)=O.FC(F)(C1C=C2C(=CC=1)N=CC=C2)C1N2N=C(C3C=CC(CCNC(=O)OC(C)(C)C)=CC=3)C=CC2=NN=1>C(O)(C(F)(F)F)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:10]([CH:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[CH:18][CH:17]=[CH:16]4)[CH3:12])=[N:9][N:8]=2)[N:7]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 702EthanolHCID 57691205N'-(6-chloropyridazin-3-yl)-2-(quinolin-6-yl)propanehydrazideHCID 67503262Tert-butyl 2-(4-(3-(difluoro(quinolin-6-yl)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)ethylcarbamate

Product 1

HCID 249687116-(1-(6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of N′-(6-chloropyridazin-3-yl)-2-(quinolin-6-yl)propanehydrazide (2700 mg, 8238 μmol) in TFA (20 mL) was heated to 120° C. with microwaves (2 bar; 10 watts) for 40 min. The solution was concentrated under reduced pressure then partitioned between 9:1 CHCl3/IPA (75 mL) and 1 M NaOH (100 mL). The aqueous layer was further extracted with 9:1 CHCl3/IPA (2×20 mL). The combined organics were dried over MgSO4 then concentrated to an amber oil under reduced pressure. The product was isolated as off white crystalline solid from ACN. MS (ESI pos. ion) m/z: 310 (MH+). Calc'd exact mass for C16H12ClN5: 309. Enantiomer resolved with: Chiralpak AD-H (3×25 cm) column using 45% ethanol (0.1% DEA)/CO2 The following compounds were prepared using same method as tert-Butyl 2-(4-(3-(difluoro(quinolin-6-yl)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)ethylcarbamate and resolved from racemic mixtures:

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. customthen partitioned between 9:1 CHCl3/IPA (75 mL) and 1 M NaOH (100 mL)
  3. extractionThe aqueous layer was further extracted with 9:1 CHCl3/IPA (2×20 mL)
  4. dry with materialThe combined organics were dried over MgSO4
  5. concentrationthen concentrated to an amber oil under reduced pressure
  6. customThe product was isolated as off white crystalline solid from ACN
  7. customwere prepared

Sources & evidence

ORD record
ord-360905db4f8541698e4bc2ab32590778
Source dataset
uspto-grants-2012_06
Patent number
US08198448B2

Reaction notes

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