Sodium Carbonate → N-[1-(4-chlorobenzyl)piperidin-4-yl]-6-chloropyridazin-3-amine

HRID 1429668Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of 1-(4-chlorobenzyl)-piperidin-4-yl amine (1 g, 4.45 mmol) (prepared by a procedure similar to that described in WO2001098273), 3,6-dichloropyridazine (670 mg, 4.45 mmol) and sodium carbonate (940 mg, 8.90 mmol) in dimethylacetamide (5 ml) was heated at 120° C. in a microwave reactor (Emrys Optimizer; 0-9 Barr) for 40 minutes. After this period, the reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was dried (MgSO4), filtered and the solvents evaporated in vacuo. Purification by reverse phase HPLC (conditions as previously described) gave E16 (228 mg, 15%). C16H18Cl2N4 requires 336; Found 337 (MH+). 1H NMR (360 MHz, CDCl3) δ1.52 (qd, J=11.5, 3.5 Hz, 2H), 2.08 (d, J=12.5 Hz, 2H), 2.16 (t, J=11.3 Hz, 2H), 2.82 (d, J=11.5 Hz, 2H), 3.48 (s, 2H), 3.77-3.87 (m, 1H), 4.55 (d, J=7.8 Hz, 1H), 6.59 (d, J=9.3 Hz, 1H), 7.14 (d, J=9.3 Hz, 1H), 7.25 (d, J=7.7 Hz, 2H), 7.29 (d, J=7.7 Hz, 2H)

Workup

waitAfter this period
extractionextracted with dichloromethane
dry with materialThe organic layer was dried (MgSO4)
filtrationfiltered
customthe solvents evaporated in vacuo
customPurification by reverse phase HPLC (conditions
customgave E16 (228 mg, 15%)

Sources & evidence

ORD record: ord-be6bfbf89bd64deaadc901757fb7af05
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940743B2

Reaction notes

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