Diisopropylethylamine → 6-fluoro-1-(1-(6-(1-methyl-1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-1H-indazole

HRID 512864Notes

Reaction equation

HRID 512864 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[CH:4][CH:3]=1.Cl[C:18]1[N:19]=[N:20][C:21]([C:24]2[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=2)=[CH:22][CH:23]=1.CCN(C(C)C)C(C)C>CS(C)=O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][N:14]([C:18]3[N:19]=[N:20][C:21]([C:24]4[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=4)=[CH:22][CH:23]=3)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 539239646-fluoro-1-(piperidin-4-yl)-1H-indazoleHCID 545956073-Chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine

Product 1

HCID 763110986-fluoro-1-(1-(6-(1-methyl-1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-1H-indazole

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

6-Fluoro-1-(piperidin-4-yl)-1H-indazole (260 mg, 1.19 mmol), 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine (230 mg, 1.19 mmol) and DIEA (269 uL) in DMSO (4 ml) under Ar were heated in a microwave reactor at 200° C. for 1 hour. After removal of most of the DMSO in vacuo, water (10 mL) was added and the aqueous layer extracted several times with CHCl3 (50 mL). The organic layer was washed with brine, dried (MgSO4), decolorized with NORITE, filtered and the solvent removed in vacuo. The resulting residue was purified via ISCO column chromatography (Amine “Redisep” 14 gram column eluded 0-100% EtOAc/hexane over 20 column volumes), then re-crystallized from DCM with heptanes to yield 6-fluoro-1-(1-(6-(1-methyl-1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-1H-indazole.

Workup

  1. customAfter removal of most of the DMSO in vacuo, water (10 mL)
  2. additionwas added
  3. extractionthe aqueous layer extracted several times with CHCl3 (50 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe resulting residue was purified via ISCO column chromatography (Amine “Redisep” 14 gram column eluded 0-100% EtOAc/hexane over 20 column volumes)
  9. customre-crystallized from DCM with heptanes

Sources & evidence

ORD record
ord-8875cd278f3a47ff88de0577b4d32e7d
Source dataset
uspto-grants-2015_08
Patent number
US09102669B2

Reaction notes

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