Hydrochloric Acid → 5-(3-amino-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol

HRID 1027183Notes

Reaction equation

HRID 1027183 reaction equation
[NH2:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[N:18]=[N:17][C:16]([N:19]([CH3:30])[CH:20]4[CH2:25][C:24]([CH3:27])([CH3:26])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]4)=[CH:15][CH:14]=3)=[C:9]([O:31]C)[CH:8]=2)[N:3]=1.C([O-])([O-])=O.[K+].[K+].C1(S)C=CC=CC=1.Cl>CN1C(=O)CCC1>[NH2:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[N:18]=[N:17][C:16]([N:19]([CH3:30])[CH:20]4[CH2:25][C:24]([CH3:26])([CH3:27])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]4)=[CH:15][CH:14]=3)=[C:9]([OH:31])[CH:8]=2)[N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7969Thiophenol2×HCID 11430Potassium Carbonate2×HCID 867105776-(4-(3-amino-1H-pyrazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

Product 1

HCID 1363771425-(3-amino-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenolYield 72.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
190 °C

Procedure

A degassed mixture of 6-(4-(3-amino-1H-pyrazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (135 mg, 0.310 mmol), K2CO3 (42.8 mg, 0.310 mmol) and thiophenol (0.032 mL, 0.310 mmol) in NMP (2 mL) was heated at 190° C. under microwave radiation for 20 min. After addition of another 0.05 mmol of thiophenol and K2CO3, the mixture was heated at 190° C. under microwave radiation for another 10 min. The mixture was acidified to pH 2-3 with 1 M HCl aqueous solution, then loaded on a 5 g SCX column. The column was washed with MeOH and eluted with 2 N NH3 in MeOH. The collected fractions were concentrated and dissolved in a mixture of MeOH and DMSO, then purified by preparative HPLC to give 95 mg of 5-(3-amino-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol as a dark yellow solid. LCMS Rt=0.47 min (LCMS method Q), MS (M+1)=422.3, HRMS: 422.2672 [M+H+].

Workup

  1. temperaturethe mixture was heated at 190° C. under microwave radiation for another 10 min
  2. washThe column was washed with MeOH
  3. washeluted with 2 N NH3 in MeOH
  4. concentrationThe collected fractions were concentrated
  5. dissolutiondissolved in a mixture of MeOH and DMSO
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-1821ba9ef391475f9d8c1232f37664cc
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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