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

HRID 1258158Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 6-chloro-pyridazine-3-carbonitrile (D4) (1.32 g, 9.46 mmol), 1-(3,4,5-trifluoro-benzyl)-piperidin-4-ylamine (D8) (2.10 g, 8.6 mmol) and diisopropylethylamine (2.25 ml, 12.9 mmol) in acetonitrile (12 ml) was stirred at 120° C. for 20 min., under microwave irradiation (Milestone MW-oven). Dichloromethane, water and a saturated solution of sodium carbonate were then added. The organic layers were filtered over cotton, evaporated in vacuo and the residue was purified by column chromatography (silica gel; 0-2% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo. The residue was precipitated from diisopropyl ether to yield E18 (2.210 g, 74%) as a solid. C17H16F3N5 requires 347. Found 348 (MH+); mp: 185° C.

Workup

filtrationThe organic layers were filtered over cotton
customevaporated in vacuo
customthe residue was purified by column chromatography (silica gel; 0-2% ammonia in methanol (7M)/dichloromethane)
customThe desired fractions were collected
customevaporated in vacuo
customThe residue was precipitated from diisopropyl ether

Sources & evidence

ORD record: ord-b37c9399d4f249f2a91a78c9019f2b47
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08466153B2

Reaction notes

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