Water → 6-chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine

HRID 1852957Notes

Reaction equation

HRID 1852957 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.CC1(C)C(C)(C)OB([C:18]2[CH:19]=[N:20][N:21]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH:22]=2)O1.[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>[Cl:9][C:4]1[N:3]=[C:2]([C:18]2[CH:19]=[N:20][N:21]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH:22]=2)[N:7]=[C:6]([NH2:8])[CH:5]=1.[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[C:4]([C:18]2[CH:19]=[N:20][N:21]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH:22]=2)[N:3]=1

Participants

8

Reactant 5

HCID 962WaterHCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 823874-Pyrimidinamine, 2,6-dichloro-HCID 574776664-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole

Product 2

HCID 866852946-chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amineYield 50.3%HCID 866852992-chloro-6-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amineYield 37.2%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
50 °C

Procedure

2,6-Dichloropyrimidin-4-amine (4.00 g, 24.4 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (Preparation E; 14.0 g, 36.6 mmol) and K3PO4 (15.5 g, 73.2 mmol) were suspended in dioxane (120 mL, 24.4 mmol) and H2O (4.39 mL, 244 mmol). After degassing under nitrogen, Pd(PPh3)4 (1.41 g, 1.22 mmol) was added and the reaction sealed and stirred at 50° C. for 15 hours. After cooling, the reaction mixture was partitioned between saturated aqueous NaHCO3 and EtOAc. The organics were washed with water, brine, dried with MgSO4, filtered and concentrated under reduced pressure to afford the crude material as a thick yellow orange oil. The crude mixture was purified by silica chromatography using a 20-100% EtOAc/Hexanes gradient to afford 6-chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine (4.00 g, 50.3%) and 2-chloro-6-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine (2.96 g, 37.2% yield). MS (apci) m/z=326.1 (M+H). The structure and regioisomer of products were confirmed by observed nOe.

Workup

  1. customAfter degassing under nitrogen
  2. customthe reaction sealed
  3. temperatureAfter cooling
  4. customthe reaction mixture was partitioned between saturated aqueous NaHCO3 and EtOAc
  5. washThe organics were washed with water, brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto afford the crude material as a thick yellow orange oil
  10. customThe crude mixture was purified by silica chromatography

Sources & evidence

ORD record
ord-8d825562ebda41fc87bf9fb0c163f609
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

Loading…