Hydrochloric Acid → HCID 136377170, compound

HRID 1027283Notes

Reaction equation

HRID 1027283 reaction equation
[ClH:1].[F:2][C:3]1[C:4]([C:18]2[N:19]=[N:20][C:21]([N:24]([CH3:35])[CH:25]3[CH2:30][C:29]([CH3:32])([CH3:31])[NH:28][C:27]([CH3:34])([CH3:33])[CH2:26]3)=[CH:22][CH:23]=2)=[C:5]([OH:17])[CH:6]=[C:7]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([O:15]C)[CH:10]=2)[CH:8]=1.Cl.N1C=CC=CC=1.Cl>CO.CS(C)=O>[ClH:1].[F:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=2)[CH:6]=[C:5]([OH:17])[C:4]=1[C:18]1[N:19]=[N:20][C:21]([N:24]([CH3:35])[CH:25]2[CH2:30][C:29]([CH3:31])([CH3:32])[NH:28][C:27]([CH3:34])([CH3:33])[CH2:26]2)=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10176127Pyridinium chlorideHCID 136377172HCID 136377172, compound

Product 1

HCID 136377170HCID 136377170, compoundYield 30.7%

Reagents, catalysts & solvents 1

HCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

3-Fluoro-5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol hydrochloride salt (Example 40-1, 10 mg, 0.02 mmol) and pyridine hydrochloride (50 mg, 0.43 mmol) were heated at 170° C. for 15 minutes in a Biotage® Initiator microwave reactor. The reaction mixture was diluted with MeOH/DMSO, and purified via reverse phase preparative HPLC (10 to 45% 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 and the resulting solid was suspended in CH3CN/H2O (3/1 mL). 1 M aqueous HCl (3 equivalents) was added and solvent was concentrated in vacuo to afford the title compound as a yellow solid (3 mg, 26%). LCMS Rt=0.47 min [Method Q]; [M+H]: 452.3; 1H NMR (400 MHz, MeOD) δ 8.28 (d, J=10.0 Hz, 1H), 8.07 (d, J=10.0 Hz, 1H), 7.69 (d, J=6.5 Hz, 1H), 7.25 (dd, J=11.0, 1.5 Hz, 1H), 7.19 (s, 1H), 6.89 (s, 1H), 6.85 (dd, J=6.5, 1.5 Hz, 1H), 5.07 (bs, 1H), 3.21 (s, 3H), 2.20-2.00 (m, 4H), 1.66 (s, 6H), 1.59 (s, 6H).

Workup

  1. custompurified via reverse phase preparative HPLC (10 to 45% acetonitrile in water, 0.1% trifluoroacetic acid as modifier)
  2. additionThe appropriate fractions containing product
  3. concentrationThe solvent was concentrated in vacuo
  4. concentrationsolvent was concentrated in vacuo

Sources & evidence

ORD record
ord-153c9a9c7b4244ea8d9601f820d5c4d1
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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