1-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → (Rac)-3-[1-(3-methyl-3h-benzoimidazol-5-yl)-ethyl]-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1h-pyrazol-4-yl}-imidazo[1,2-b]pyridazine

HRID 69229Notes

Reaction equation

HRID 69229 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:22]=[CH:21][C:16]4[N:17]=[CH:18][N:19]([CH3:20])[C:15]=4[CH:14]=3)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[O:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[O:29][CH2:30][CH2:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1>COCCOC>[CH3:20][N:19]1[C:15]2[CH:14]=[C:13]([CH:11]([C:8]3[N:6]4[N:7]=[C:2]([C:35]5[CH:34]=[N:33][N:32]([CH2:31][CH2:30][O:29][CH:24]6[CH2:25][CH2:26][CH2:27][CH2:28][O:23]6)[CH:36]=5)[CH:3]=[CH:4][C:5]4=[N:10][CH:9]=3)[CH3:12])[CH:22]=[CH:21][C:16]=2[N:17]=[CH:18]1

Participants

4

Reactant 2

HCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 87524205(Rac)-6-chloro-3-[1-(3-methyl-3h-benzoimidazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine

Product 1

HCID 68633396(Rac)-3-[1-(3-methyl-3h-benzoimidazol-5-yl)-ethyl]-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1h-pyrazol-4-yl}-imidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

(rac)-6-Chloro-3-[1-(3-methyl-3H-benzoimidazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (Stage 185.2, 525 mg, 1.381 mmol) was introduced in a microwave reactor together with 1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3 ,2]dioxaborolan-2-yl)-1H-pyrazole (Stage 171.4, 667 mg, 2.071 mmol) and DME (9 mL). The mixture was purged with Argon for 5 min. Pd(PPh3)2Cl2 (38.8 mg) and 2 M K2CO3 (1.864 mL) were added and the mixture was flushed with Argon before being sealed. It was then heated at 90° C. for 4,5 h. The RM was diluted with EtOAc and washed with water, brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with 40 g RediSep® silica gel column, DCM/MeOH=100:0->92:8 in 25 min). The collected fractions containing product were evaporated and the residue was dried under vacuum to afford the title compound as an oil (tR 2.39 min (conditions 8), MH+=472).

Workup

  1. customThe mixture was purged with Argon for 5 min
  2. additionPd(PPh3)2Cl2 (38.8 mg) and 2 M K2CO3 (1.864 mL) were added
  3. customthe mixture was flushed with Argon
  4. custombefore being sealed
  5. additionThe RM was diluted with EtOAc
  6. washwashed with water, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with 40 g RediSep® silica gel column, DCM/MeOH=100:0->92:8 in 25 min)
  11. additionThe collected fractions containing product
  12. customwere evaporated
  13. customthe residue was dried under vacuum

Sources & evidence

ORD record
ord-e894ed16d7404d4bb8d61c2d32eb7ede
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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