4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine Chemical Properties

Boiling point:

409.7±47.0 °C(Predicted)

Density 

1.11

storage temp. 

Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

pka

4.19±0.10(Predicted)

Appearance

Off-white to light brown Solid

Water Solubility 

Slightly soluble in water.

InChI

InChI=1S/C11H18BN3O2/c1-7-8(6-14-9(13)15-7)12-16-10(2,3)11(4,5)17-12/h6H,1-5H3,(H2,13,14,15)

InChIKey

SYJMHOBGFXCKRG-UHFFFAOYSA-N

SMILES

C1(N)=NC=C(B2OC(C)(C)C(C)(C)O2)C(C)=N1

CAS DataBase Reference

944401-55-2

Safety Information

TSCA 

N

HS Code 

2933599590

4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine Usage And Synthesis

Uses

2-Amino-4-methylpyrimidine-5-boronic acid pinacol ester is used as pharmaceutical intermediate.

Synthesis

Using 2-amino-4-methyl-5-bromopyrimidine (5.0 g, 26 mmol) and pinacol ester of bisboronic acid (7.43 g, 29.2 mmol) as raw materials, the two were mixed with potassium acetate (7.83 g, 79.8 mmol) in dioxane (140 mL) under nitrogen protection, and stirred for 20 minutes. Subsequently, 1,1'-bis(diphenylphosphino)ferrocene palladium(II) chloride dichloromethane adduct (1.08 g, 1.33 mmol) was added to the reaction mixture. The reaction mixture was heated to 115 °C under nitrogen protection and kept for 18 hours. After completion of the reaction, the mixture was cooled, EtOAc was added, sonicated and filtered. The solid was washed with additional EtOAc. The organic extracts were combined, washed with water, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography using a 20-100% EtOAc/hexane gradient elution to give 4.5 g 2-amino-4-methylpyrimidine-5-boronic acid pinacol ester (yield: 74%). The structure of the product was confirmed by 1H-NMR (DMSO, 400 MHz) and mass spectrometry (ESI): 1H-NMR δ 8.28 (s, 1H), 6.86 (br s, 2H), 2.35 (s, 3H), 1.25 (s, 12H); MS (ESI) m/e 236.15 (M + H+), 154.07.

References

[1] Patent: WO2012/82997, 2012, A1. Location in patent: Page/Page column 83
[2] Patent: US2014/65136, 2014, A1. Location in patent: Paragraph 0198; 0199
[3] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 4, p. 351 - 356
[4] Patent: WO2009/146406, 2009, A1. Location in patent: Page/Page column 69-70
[5] Patent: WO2009/13348, 2009, A2. Location in patent: Page/Page column 67

4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine(944401-55-2)Related Product Information

• Pyrimidine