5-Chloropyridazin-4-amine → 5-(4-((3,3-Difluoropyrrolidin-1-yl)methyl)piperidin-1-yl)pyridazin-4-amine

HRID 1850690Notes

Reaction equation

Cl[C:2]1[C:3]([NH2:8])=[CH:4][N:5]=[N:6][CH:7]=1.[F:9][C:10]1([F:22])[CH2:14][CH2:13][N:12]([CH2:15][CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH2:11]1>CN1C(=O)CCC1>[F:22][C:10]1([F:9])[CH2:14][CH2:13][N:12]([CH2:15][CH:16]2[CH2:21][CH2:20][N:19]([C:2]3[C:3]([NH2:8])=[CH:4][N:5]=[N:6][CH:7]=3)[CH2:18][CH2:17]2)[CH2:11]1

Participants

Conditions

Temperature: 170 °C

Procedure

A mixture of 5-chloropyridazin-4-amine (50 mg, 0.3860 mmol), 4-[(3,3-difluoropyrrolidin-1-yl)methyl]piperidine (197.1 mg, 0.9650 mmol) in NMP (10 mL) were heated under microwave conditions at 170° C. for 7 hours. The reaction was passed through a 10 g SCX-2 cartridge and washed with MeOH/DCM mixtures. The product was eluted by washing the cartridge with 2M NH3 in MeOH/DCM mixtures. The solvent was removed in vacuo and the residue was purified by column chromatography (ISCO Companion, 12 g column, eluting with 0 to 10% MeOH/DCM, loaded in DCM) to give the sub-title product as a beige solid (27 mg, 23% Yield). 1H NMR (500 MHz, DMSO) δ 8.46 (d, 1H), 8.41 (s, 1H), 5.85 (s, 2H), 3.20 (d, 2H), 2.87 (t, 2H), 2.69 (t, 2H), 2.59 (td, 2H), 2.34 (d, 2H), 2.24 (tt, 2H), 1.83-1.74 (m, 2H), 1.65-1.53 (m, 1H), 1.43-1.30 (m, 2H); 19F NMR (471 MHz, DMSO) δ −90.81; LC-MS ES+: 298.1, ES−: 296.1.

Workup

washwashed with MeOH/DCM mixtures
washThe product was eluted
washby washing the cartridge with 2M NH3 in MeOH/DCM mixtures
customThe solvent was removed in vacuo
customthe residue was purified by column chromatography (ISCO Companion, 12 g column, eluting with 0 to 10% MeOH/DCM, loaded in DCM)

Sources & evidence

ORD record: ord-ec3061d578f84e68b32fc7662b8836f1
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08957078B2

Reaction notes

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