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

HRID 1258155Notes

Reaction equation

HRID 1258155 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:25])[CH:24]=1)[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:10][C:11]1[CH:12]=[C:13]([CH:22]=[C:23]([F:25])[CH:24]=1)[CH2:14][N:15]1[CH2:16][CH2:17][CH:18]([NH:21][C:2]2[N:7]=[N:6][C:5]([C:8]#[N:9])=[CH:4][CH:3]=2)[CH2:19][CH2:20]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 133828716-Chloropyridazine-3-carbonitrileHCID 221824001-[(3,5-Difluorophenyl)methyl]piperidin-4-amine

Product 1

HCID 249891996-[1-(3,5-Difluoro-benzyl)-piperidin-4-ylamino]-pyridazine-3-carbonitrileYield 60.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-chloro-pyridazine-3-carbonitrile (D4) (1.74 g, 12.46 mmol), 1-(3,5-difluoro-benzyl)-piperidin-4-ylamine (D5) (2.35 g, 10.386 mmol) and diisopropylethylamine (2.71 ml, 15.58 mmol) in acetonitrile (30 ml) was stirred at 120° C. for 40 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; 0-1.5% ammonia in methanol (7 M)/dichloromethane). The desired fractions were collected and evaporated in vacuo. The residue was precipitated in heptane to yield E15 (2.065 g, 60%) as a solid. C17H17F2N5 requires 329. Found 330 (MH+); mp: 187.9° C.

Workup

  1. filtrationThe organic layers were filtered over cotton
  2. customevaporated in vacuo
  3. customthe residue was purified by column chromatography (silica gel; 0-1.5% ammonia in methanol (7 M)/dichloromethane)
  4. customThe desired fractions were collected
  5. customevaporated in vacuo
  6. customThe residue was precipitated in heptane

Sources & evidence

ORD record
ord-d2137ceb23bf4496bde63be1f388efed
Source dataset
uspto-grants-2013_06
Patent number
US08466153B2

Reaction notes

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