6-Chloro-3-((6-fluoro-1-methyl-1H-indazol-5-yl)methyl)imidazo[1,2-b]pyridazine → 3-(6-Fluoro-1-methyl-1H-indazol-5-ylmethyl)-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazine

HRID 69284Notes

Reaction equation

HRID 69284 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][C:20]=3[F:21])[N:17]([CH3:22])[N:16]=[CH:15]4)=[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>[F:21][C:20]1[CH:19]=[C:18]2[C:14]([CH:15]=[N:16][N:17]2[CH3:22])=[CH:13][C:12]=1[CH2:11][C:8]1[N:6]2[N:7]=[C:2]([C:35]3[CH:34]=[N:33][N:32]([CH2:31][CH2:30][O:29][CH:24]4[CH2:25][CH2:26][CH2:27][CH2:28][O:23]4)[CH:36]=3)[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1

Participants

4

Reactant 2

HCID 581906096-Chloro-3-((6-fluoro-1-methyl-1H-indazol-5-yl)methyl)imidazo[1,2-b]pyridazineHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 690748973-(6-Fluoro-1-methyl-1H-indazol-5-ylmethyl)-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

Procedure

6-Chloro-3-(6-fluoro-1-methyl-1H-indazol-5-ylmethyl)-imidazo[1,2-b]pyridazine (Stage 281.2, 268 mg, 849 μmol) was introduced in a microwave reactor together with 1-[2-(tetrahydropyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (Stage 171.4, 410 mg, 1.273 mmol) and DME (5 mL). The mixture was purged with Argon for 5 min. Tetrakis-(triphenylphosphine)-palladium (39.2 mg) and 2 M Na2CO3 (1.528 mL) were added and the mixture was flushed with argon before being sealed. The RM was submitted to microwave irradiation at 150° C. 30 min. 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->94:6 in 45 min). The collected fractions containing product were evaporated and the residue was dried under vacuum to afford the title compound as an oil (tR 1.13 min (conditions 2), MH+=476)

Workup

  1. customThe mixture was purged with Argon for 5 min
  2. additionTetrakis-(triphenylphosphine)-palladium (39.2 mg) and 2 M Na2CO3 (1.528 mL) were added
  3. customthe mixture was flushed with argon
  4. custombefore being sealed
  5. customirradiation at 150° C
  6. custom30 min
  7. additionThe RM was diluted with EtOAc
  8. washwashed with water, brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with 40 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 45 min)
  13. additionThe collected fractions containing product
  14. customwere evaporated
  15. customthe residue was dried under vacuum

Sources & evidence

ORD record
ord-b4f8feb95ec0439887cd2d32385dd82e
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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