Pyridinium chloride → HCID 136377154, compound

HRID 1027223Notes

Reaction equation

HRID 1027223 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([O:8]C)[C:5]([C:10]2[N:15]=[N:14][C:13]([N:16]([CH3:27])[CH:17]3[CH2:22][C:21]([CH3:24])([CH3:23])[NH:20][C:19]([CH3:26])([CH3:25])[CH2:18]3)=[CH:12][CH:11]=2)=[C:4]([F:28])[CH:3]=1.Cl.N1C=CC=CC=1>CO.CS(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([F:28])[C:5]([C:10]2[N:15]=[N:14][C:13]([N:16]([CH3:27])[CH:17]3[CH2:18][C:19]([CH3:25])([CH3:26])[NH:20][C:21]([CH3:24])([CH3:23])[CH2:22]3)=[CH:12][CH:11]=2)=[C:6]([OH:8])[CH:7]=1

Participants

4

Reactant 2

HCID 10176127Pyridinium chlorideHCID 86710627HCID 86710627, compound

Product 1

HCID 136377154HCID 136377154, compoundYield 24.1%

Reagents, catalysts & solvents 1

HCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

6-(4-Bromo-2-fluoro-6-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (0.81 g, 1.80 mmol) and pyridine hydrochloride (1.65 g, 14.3 mmol) were heated to 190° C. for 45 min in a Biotage® Initiator microwave reactor. The reaction mixture was diluted in MeOH/DMSO, and purified via reverse phase preparative HPLC (5 to 95% acetonitrile in water, 0.1% trifluoroacetic acid as modifier). The appropriate fractions containing product were free based by catch and release using SiliaBond Propylsulphonic Acid® (4 eq, methanol as eluent and a 2 N ammonia solution in MeOH to release the material). The solvent was concentrated in vacuo to afford 5-bromo-3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol as a beige solid (0.19 g, 23%). [M+H]: 439.2; 1H NMR (400 MHz, MeOD) δ 7.96 (d, J=10.0 Hz, 1H), 7.27 (d, J=10.0 Hz, 1H), 6.97 (t, J=2.0 Hz, 1H), 6.89 (dd, J=11.5, 2.0 Hz, 1H), 5.07-5.35 (m, 1H), 3.02 (s, 3H), 1.73 (dd, J=12.5, 3.5 Hz, 2H), 1.62 (t, J=12.5 Hz, 2H), 1.41 (s, 6H), 1.27 (s, 6H).

Workup

  1. custompurified via reverse phase preparative HPLC (5 to 95% acetonitrile in water, 0.1% trifluoroacetic acid as modifier)
  2. additionThe appropriate fractions containing product
  3. concentrationThe solvent was concentrated in vacuo

Sources & evidence

ORD record
ord-4157ef2f54234fcfa80b5c735d49ef00
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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