Potassium Phosphate, Tribasic → HCID 86710670, compound

HRID 1027259Notes

Reaction equation

HRID 1027259 reaction equation
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[C:5]([O:17][CH3:18])=[CH:4][C:3]=1[C:19]1[CH:20]=[N:21][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:23]=1.Cl[C:32]1[N:37]=[N:36][C:35]([N:38]([CH3:49])[CH:39]2[CH2:44][C:43]([CH3:46])([CH3:45])[NH:42][C:41]([CH3:48])([CH3:47])[CH2:40]2)=[CH:34][CH:33]=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>[F:1][C:2]1[CH:7]=[C:6]([C:32]2[N:37]=[N:36][C:35]([N:38]([CH3:49])[CH:39]3[CH2:44][C:43]([CH3:45])([CH3:46])[NH:42][C:41]([CH3:48])([CH3:47])[CH2:40]3)=[CH:34][CH:33]=2)[C:5]([O:17][CH3:18])=[CH:4][C:3]=1[C:19]1[CH:20]=[N:21][N:22]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH:23]=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 86710671HCID 86710671, compound

Product 1

HCID 86710670HCID 86710670, compoundYield 101.7%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a microwave vial was added tert-butyl 4-(2-fluoro-5-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazole-1-carboxylate (98 mg, 0.23 mmol), 6-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (Intermediate 1-1, 66.3 mg, 0.23 mmol), potassium phosphate (199 mg, 0.94 mmol), Pd2(dba)3 (21.5 mg, 0.02 mmol), and SPhos (9.62 mg, 0.02 mmol), followed by addition of 1,4-dioxane (0.4 mL)/H2O (0.9 mL). The vial was purged with N2 for 5 minutes and then heated at 100° C. in the microwave for one hour. The reaction mixture was concentrated in vacuo. The crude material was adjusted to pH 3 using 1 M HCl aqueous solution and loaded on an SCX column. The crude material was washed with methanol then eluted with 2 N ammonia in methanol. The product-containing fractions were concentrated to afford tert-butyl 4-(2-fluoro-5-methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1H-pyrazole-1-carboxylate (126 mg) MS [M+H+]=539.2.

Workup

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

Sources & evidence

ORD record
ord-6d94894bf4fc497fbd4f34d490b3f509
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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