4-(4,4,5,5-TETRAMETHYL-[1,3,2]DIOXABOROLAN-2-YL)-3,6-DIHYDRO-2H-PYRIDINE-1-CARBOXYLIC ACID BENZYL ESTER Chemical Properties

Melting point:

88-90℃

Boiling point:

418.2±55.0 °C(Predicted)

Density 

1.13

storage temp. 

Sealed in dry,Store in freezer, under -20°C

pka

-1.26±0.40(Predicted)

form 

Solid

color 

Off-white

InChI

InChI=1S/C19H26BNO4/c1-18(2)19(3,4)25-20(24-18)16-10-12-21(13-11-16)17(22)23-14-15-8-6-5-7-9-15/h5-10H,11-14H2,1-4H3

InChIKey

QDSFHRPYZPQWEJ-UHFFFAOYSA-N

SMILES

C1N(C(OCC2=CC=CC=C2)=O)CC=C(B2OC(C)(C)C(C)(C)O2)C1

CAS DataBase Reference

286961-15-7

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-37

TSCA 

No

HS Code 

2933399990

4-(4,4,5,5-TETRAMETHYL-[1,3,2]DIOXABOROLAN-2-YL)-3,6-DIHYDRO-2H-PYRIDINE-1-CARBOXYLIC ACID BENZYL ESTER Usage And Synthesis

Uses

Benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate is a reactant used in the synthesis of potent and orally bioavailable inhibitors of βII tryptase used in the treatment of allergic diseases.

Synthesis

N-Benzyloxycarbonyl-3,6-dihydro-2H-pyridine-4-boronic acid pinacol ester was synthesized from bis(pinacolato) boronic acid and the compound (CAS: 286961-24-8) according to the method reported in Tetrahedron Lett. The steps were as follows: bis(pinacolato)ethylborane (338 mg, 1.33 mmol), potassium acetate (356 mg, 3.63 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (PdCl2dppf; 30 mg, 0.04 mmol), and 1,1'-bis(diphenylphosphino)ferrocene ( 20 mg, 0.04 mmol), followed by addition of the product of Example 58A (440 mg, 1.21 mmol) in degassed 1,4-dioxane (7 mL). The reaction mixture was heated at 80 °C for 16 h, after which it was cooled to 23 °C, diluted with water and extracted with dichloromethane (3×). The organic phases were combined, dried over anhydrous sodium sulfate, filtered and the filtrate concentrated under reduced pressure. The residue was purified by fast column chromatography on silica gel (eluent: 20% ethyl acetate/hexane) to afford the target product N-benzyloxycarbonyl-3,6-dihydro-2H-pyridine-4-boronic acid pinacol ester (323 mg, 78% yield). The product was confirmed by 1H NMR (300 MHz, CDCl3) and mass spectrometry (ESI): 1H NMR δ 1.25 (s, 12H), 2.24 (m, 2H), 3.52 (dd, 2H, J = 5.7, 5.7 Hz), 4.03 (dd, 2H, J = 6 Hz), 5.14 (s, 2H), 6.46 (br m, 1H), 7.32 (m, 5H); MS (ESI) m/e 344 (M + H)+.

References

[1] Tetrahedron Letters, 2000, vol. 41, # 19, p. 3705 - 3708
[2] Journal of Medicinal Chemistry, 2006, vol. 49, # 25, p. 7450 - 7465
[3] Patent: US2003/229094, 2003, A1. Location in patent: Page 76
[4] Patent: US2003/232836, 2003, A1. Location in patent: Page 52
[5] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 8, p. 2859 - 2872