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

HRID 1027182Notes

Reaction equation

HRID 1027182 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:18]2[CH:22]=[CH:21][C:20]([NH2:23])=[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.C([O-])(O)=O.[Na+].CCOCC>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:23][C:20]1[CH:21]=[CH:22][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)[N:19]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 516892Sodium BicarbonateHCID 867105396-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2×HCID 867105781-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazol-3-amine

Product 1

HCID 867105776-(4-(3-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 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A degassed reaction mixture of 1-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazol-3-amine (474 mg, 1.505 mmol), 6-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine Intermediate 1-1 (370 mg, 1.308 mmol) tetrakis(triphenylphosphine)palladium(0) (76 mg, 0.065 mmol) and 1 M NaHCO3 (330 mg, 3.92 mmol) in 1,4-dioxane (7 mL) and water (2.3 mL) was heated at 100° C. for 14 h. After cooling to RT, the mixture was filtered through celite, washed with EtOAc, and the filtrate was concentrated. The residue was suspended in MeOH, acidified to pH 2-3 using 1 M aqueous HCl and loaded on a 10 g SCX column. The column was washed with MeOH, then eluted with 2 N NH3 in MeOH. The collected fractions were concentrated to give a light brown oil, which was treated with ether and concentrated to give 570 mg of 6-(4-(3-amino-1H-pyrazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine as a light brown solid.

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe mixture was filtered through celite
  3. washwashed with EtOAc
  4. concentrationthe filtrate was concentrated
  5. washThe column was washed with MeOH
  6. washeluted with 2 N NH3 in MeOH
  7. concentrationThe collected fractions were concentrated
  8. customto give a light brown oil, which
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-f83da82e58764fef9a9c7882683aba76
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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