Cesium carbonate → (6-(5-Cyclopropylisoxazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanamine

HRID 1513831Notes

Reaction equation

HRID 1513831 reaction equation
[CH:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([CH2:12][NH:13]C(=O)OC(C)(C)C)=[N:10][N:11]=2)[N:8]=1)=[CH2:2].C[C:22]1(C)[C:26]([CH3:28])([CH3:27])OB(C=C)[O:23]1.ClC1C=CC2[N:37](C(CNC(=O)OC(C)(C)C)=NN=2)N=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[CH:26]1([C:22]2[O:23][N:37]=[C:1]([C:3]3[CH:4]=[CH:5][C:6]4[N:7]([C:9]([CH2:12][NH2:13])=[N:10][N:11]=4)[N:8]=3)[CH:2]=2)[CH2:28][CH2:27]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 57691367Tert-butyl (6-vinyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamateHCID 57691389tert-Butyl ((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)carbamate

Product 1

HCID 57691172(6-(5-Cyclopropylisoxazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanamineYield 95%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-butyl (6-vinyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate. To an argon purged flask were added 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (7.65 ml, 45.1 mmol), tert-butyl (6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (3.20 g, 11.3 mmol), cesium carbonate (11.0 g, 33.8 mmol), and PdCl2(dppf)-CH2Cl2 (0.461 g, 0.564 mmol). The mixture was dissolved in 38 mL of dioxane and 4 mL of water (0.25M 10:1) and was heated to 80° C. for 12 h. The mixture was cooled to room temperature, concentrated, and purified directly via MPLC (DCM/MeOH+1% NH4OH) to afford the title compound (3.0 g, 95% yield).

Workup

  1. concentrationconcentrated
  2. custompurified directly via MPLC (DCM/MeOH+1% NH4OH)

Sources & evidence

ORD record
ord-ca2cadbe336e465aa7cff932a1c586a5
Source dataset
uspto-grants-2012_07
Patent number
US08217177B2

Reaction notes

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