Sodium Carbonate → 6-[1-(3,5-Difluoro-benzyl)-piperidin-4-ylamino]-4,5-dimethyl-pyridazine-3-carbonitrile

HRID 1258159Notes

Reaction equation

Cl[C:2]1[N:7]=[N:6][C:5]([C:8]#[N:9])=[C:4]([CH3:10])[C:3]=1[CH3:11].[F:12][C:13]1[CH:14]=[C:15]([CH:24]=[C:25]([F:27])[CH:26]=1)[CH2:16][N:17]1[CH2:22][CH2:21][CH:20]([NH2:23])[CH2:19][CH2:18]1.C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.ClCCl>[F:12][C:13]1[CH:14]=[C:15]([CH:24]=[C:25]([F:27])[CH:26]=1)[CH2:16][N:17]1[CH2:18][CH2:19][CH:20]([NH:23][C:2]2[N:7]=[N:6][C:5]([C:8]#[N:9])=[C:4]([CH3:10])[C:3]=2[CH3:11])[CH2:21][CH2:22]1

Participants

Conditions

Temperature: 180 °C

Procedure

A mixture of 6-chloro-4,5-dimethyl-pyridazine-3-carbonitrile (D11) (0.120 g, 0.72 mmol), 1-(3,5-difluoro-benzyl)-piperidin-4-ylamine (D5) (0.194 g, 0.86 mmol) and diisopropylethylamine (0.188 ml, 1.08 mmol) in acetonitrile was stirred at 180° C. for 20 min., under microwave irradiation (Biotage MW-oven), and then again at 180° C. for additional 30 min. Dichloromethane, water and a saturated solution of sodium carbonate were then added. The organic phase was separated, filtered over cotton and evaporated in vacuo. The residue was purified by column chromatography (silica gel; 0-1% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and the solvent evaporated in vacuo to yield E19 (0.108 g, 42%) as a solid. C19H21F2N5 requires 357. Found 358 (MH+).

Workup

waitagain at 180° C. for additional 30 min
customThe organic phase was separated
filtrationfiltered over cotton
customevaporated in vacuo
customThe residue was purified by column chromatography (silica gel; 0-1% ammonia in methanol (7M)/dichloromethane)
customThe desired fractions were collected
customthe solvent evaporated in vacuo

Sources & evidence

ORD record: ord-d9fe36792021470db79704d6120dada9
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08466153B2

Reaction notes

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