Hydrochloric Acid → HCID 178482090, compound

HRID 1027298Notes

Reaction equation

HRID 1027298 reaction equation
[CH3:1][N:2]([CH:29]1[CH2:34][C:33]([CH3:36])([CH3:35])[NH:32][C:31]([CH3:38])([CH3:37])[CH2:30]1)[C:3]1[N:8]=[N:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:16]=[CH:17][N:18](COCC[Si](C)(C)C)[CH:19]=3)=[CH:11][C:10]=2[OH:28])=[CH:5][CH:4]=1.C(Cl)Cl.Cl.B(Br)(Br)Br>CCO>[NH:18]1[CH:19]=[C:15]([C:12]2[CH:13]=[CH:14][C:9]([C:6]3[N:7]=[N:8][C:3]([N:2]([CH3:1])[CH:29]4[CH2:34][C:33]([CH3:35])([CH3:36])[NH:32][C:31]([CH3:38])([CH3:37])[CH2:30]4)=[CH:4][CH:5]=3)=[C:10]([OH:28])[CH:11]=2)[N:16]=[CH:17]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 25134Boron tribromideHCID 1363771822-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)phenol

Product 1

HCID 178482090HCID 178482090, compoundYield 5.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

To a microwave vial containing 2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)phenol (mixture from previous step, 50 mg, 0.09 mmol) in EtOH (1.0 mL)/DCM (1.0 mL) and conc. HCl (8.5 μL) was added BBr3 (0.46 mL, 0.46 mmol). The vial was purged with N2 (2×) and the reaction mixture was heated at 110° C. in a microwave reactor for 30 min. The reaction mixture was filtered through celite (pre-packed filter funnel) with a MeOH wash. The filtrate was acidified to pH 3 using 1N HCl and purified by catch and release using SiliaBond Propylsulfonic Acid® (1 g, MeOH as eluent and a 2 N ammonia solution in MeOH to release the material). After evaporation, the material was purified via reverse phase HPLC to afford 5-(1H-imidazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol (2 mg). MS: 407.4 [M+H+]. LCMS Rt=0.40 min [Method Q]; 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.01 (d, J=9.60 Hz, 1H), 7.57-7.74 (m, 2H), 7.39 (s, 1H), 7.14-7.30 (m, 3H), 4.98 (br. s., 1H), 2.92 (s, 3H), 1.62 (d, J=13.14 Hz, 2H), 1.52 (t, J=12.38 Hz, 2H), 1.32 (s, 6H), 1.16 (s, 6H).

Workup

  1. customThe vial was purged with N2 (2×)
  2. filtrationThe reaction mixture was filtered through celite (pre-packed filter funnel) with a MeOH
  3. washwash
  4. custompurified by catch and release
  5. customAfter evaporation
  6. customthe material was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-cd2b489638a24f2a850aefc3118a09a3
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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