Water → 6-fluoro-1-(1-(6-(4-methyl-1H-imidazol-1-yl)pyridazin-3-yl)piperidin-4-yl)indoline

HRID 512838Notes

Reaction equation

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

Participants

Conditions

Temperature: 180 °C

Procedure

To a mixture of 6-fluoro-1-(piperidin-4-yl)indoline (128 mg, 0.5 mmol), 3-chloro-6-(4-methylimidazol-1-yl)pyridazine (78 mg, 0.4 mmol) in DMSO (1.5 mL) was added DIPEA (0.25 mL, 1.5 mmol). The resulting mixture was sealed and heated at 180° C. for 1.5 h under microwave irradiation. The resulting mixture was then poured into H2O (30 mL) and the aqueous layer was extracted with 10% CH2Cl2/Et2O (80 mL×4). The combined organic layer was dried (Na2SO4) and filtered. The solvent was removed and the resulting residue was purified by column (dry loading) using EtOAc then 3% MeOH/EtOAc as the eluent to yield 6-fluoro-1-(1-(6-(4-methyl-1H-imidazol-1-yl)pyridazin-3-yl)piperidin-4-yl)indoline.

Workup

customThe resulting mixture was sealed
extractionthe aqueous layer was extracted with 10% CH2Cl2/Et2O (80 mL×4)
dry with materialThe combined organic layer was dried (Na2SO4)
filtrationfiltered
customThe solvent was removed
customthe resulting residue was purified by column (dry loading)

Sources & evidence

ORD record: ord-cc306303be69495c8a958029a8661415
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102669B2

Reaction notes

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