Potassium Phosphate, Tribasic → 6-(4-(4-amino-1H-pyrazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

HRID 1027177Notes

Reaction equation

HRID 1027177 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:18]2[CH:22]=[C:21]([NH2:23])[CH:20]=[N:19]2)[CH:6]=[CH:7][C:8]=1B1OC(C)(C)C(C)(C)O1.Cl[C:25]1[N:30]=[N:29][C:28]([N:31]([CH3:42])[CH:32]2[CH2:37][C:36]([CH3:39])([CH3:38])[NH:35][C:34]([CH3:41])([CH3:40])[CH2:33]2)=[CH:27][CH:26]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.O1CCOCC1>[NH2:23][C:21]1[CH:20]=[N:19][N:18]([C:5]2[CH:6]=[CH:7][C:8]([C:25]3[N:30]=[N:29][C:28]([N:31]([CH3:42])[CH:32]4[CH2:37][C:36]([CH3:38])([CH3:39])[NH:35][C:34]([CH3:41])([CH3:40])[CH2:33]4)=[CH:27][CH:26]=3)=[C:3]([O:2][CH3:1])[CH:4]=2)[CH:22]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 867105396-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2×HCID 867105711-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazol-4-amine

Product 1

HCID 867105706-(4-(4-amino-1H-pyrazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave vial was added 1-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazol-4-amine (92 mg, 0.29 mmol), 6-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine Intermediate 1-1 (75 mg, 0.27 mmol), potassium phosphate (169 mg, 0.78 mmol), Pd2(dba)3 (12.14 mg, 0.01 mmol), and SPhos (10.89 mg, 0.03 mmol), followed by addition of 1,4-dioxane (1 mL)/H2O (0.2 mL). The vial was purged with N2 for 10 minutes and the reaction mixture was heated at 100° C. in a microwave reactor for one hour. The reaction mixture was concentrated in vacuo, then the crude material was adjusted to pH 3 using 1 M HCl aqueous solution, then loaded on an SCX column. The column was washed with methanol then eluted with 2 N ammonia in methanol. The product-containing fractions concentrated to afford 6-(4-(4-amino-1H-pyrazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (100 mg, MS: 436.4 [M+H+].).

Workup

  1. customThe vial was purged with N2 for 10 minutes
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. washThe column was washed with methanol
  4. washthen eluted with 2 N ammonia in methanol
  5. concentrationThe product-containing fractions concentrated

Sources & evidence

ORD record
ord-903094cc1547470f87cfe839bed4349a
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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