Potassium Phosphate, Tribasic → 6-(1-methyl-1H-pyrazol-4-yl)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine

HRID 1852958Notes

Reaction equation

HRID 1852958 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:12]=2)[N:5]=[C:4]([NH2:21])[CH:3]=1.[CH3:22][N:23]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[N:24]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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>[CH3:22][N:23]1[CH:27]=[C:26]([C:2]2[N:7]=[C:6]([C:8]3[CH:9]=[N:10][N:11]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:12]=3)[N:5]=[C:4]([NH2:21])[CH:3]=2)[CH:25]=[N:24]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 866852946-chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine

Product 1

HCID 674585736-(1-methyl-1H-pyrazol-4-yl)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amineYield 54.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

6-Chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine (1.00 g, 3.07 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.958 g, 4.60 mmol), K3PO4 (1.95 g, 9.21 mmol), and Pd(PPh3)4 (0.355 g, 0.307 mmol) were suspended in dioxane (15.3 mL) and H2O (0.829 mL). After de-gassing with nitrogen, the reaction mixture was heated to 100° C. overnight. After cooling, the reaction mixture was diluted in EtOAc and washed with water and brine. The organics were dried with MgSO4, filtered and concentrated down to an orange oil. Purification of the resulting crude material by silica chromatography using a gradient of 0-10% MeOH/EtOAc afforded 6-(1-methyl-1H-pyrazol-4-yl)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine (0.623 g, 1.68 mmol, 54.7% yield) as a thick yellow oil. MS (apci) m/z=372.4 (M+H).

Workup

  1. customAfter de-gassing with nitrogen
  2. temperatureAfter cooling
  3. additionthe reaction mixture was diluted in EtOAc
  4. washwashed with water and brine
  5. dry with materialThe organics were dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated down to an orange oil
  8. customPurification of the resulting crude material by silica chromatography

Sources & evidence

ORD record
ord-23d7feb8b26644a5a2986b8d4a830ea1
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

Loading…