1,2-Dimethoxyethane → (Rac)-imidazo[1,2-a]pyridin-6-yl-[6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-methanol

HRID 69166Notes

Reaction equation

HRID 69166 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[CH:15][C:16]4[N:17]([CH:19]=[CH:20][N:21]=4)[CH:18]=3)[OH:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:22][N:23]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[N:24]1.C([O-])([O-])=O.[K+].[K+].COCCOC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(Cl)Cl>[N:21]1[CH:20]=[CH:19][N:17]2[CH:18]=[C:13]([CH:11]([C:8]3[N:6]4[N:7]=[C:2]([C:26]5[CH:25]=[N:24][N:23]([CH3:22])[CH:27]=5)[CH:3]=[CH:4][C:5]4=[N:10][CH:9]=3)[OH:12])[CH:14]=[CH:15][C:16]=12

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 87523529(Rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-imidazo[1,2-a]pyridin-6-yl-methanol

Product 1

HCID 44206290(Rac)-imidazo[1,2-a]pyridin-6-yl-[6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-methanol

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A microwave tube was charged under argon atm. with (rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-imidazo[1,2-a]pyridin-6-yl-methanol (Stage 9.1, 89.9 mg, 0.3 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (62.4 mg, 0.3 mmol), Pd(PPh3)2Cl2 (6.3 mg) and 2 M K2CO3 (0.405 mL) and DME (1 mL). The mixture was heated at 80° C. for 3 h. The RM was taken up with DCM and washed with NaCl solution. After filtration of both layers, the solid part was dissolved in MeOH and evaporated to dryness. The residue was stirred in EtOAc and filtered to give the pure title compound. The organic layer of the first filtrate was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=95:5—>80:20) to afford a second batch of the title compound (tR 2.57 min (conditions 3), MH+=346.2)

Workup

  1. additionA microwave tube was charged under argon atm
  2. washwashed with NaCl solution
  3. filtrationAfter filtration of both layers
  4. dissolutionthe solid part was dissolved in MeOH
  5. customevaporated to dryness
  6. filtrationfiltered

Sources & evidence

ORD record
ord-81bd8a6f8f264b8e9211197c2b71b618
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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