Tert-butyl 2,4-dichloro-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7(6H)-carboxylate Chemical Properties

Boiling point:

436.6±45.0 °C(Predicted)

Density 

1.311±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

-1.68±0.20(Predicted)

Appearance

White to off-white Solid

Safety Information

HS Code 

2933998090

Tert-butyl 2,4-dichloro-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7(6H)-carboxylate Usage And Synthesis

Synthesis

The general procedure for the synthesis of 7-BOC-2,4-dichloro-5,6,8,9-pyrimido[4,5-d]azepine-7-carboxylic acid from tert-butyl 4-oxo-2-thioxo-1,2,3,4,5,6,8,9-octahydro-7H-pyrimido[4,5-D]aza-7-carboxylate and di-tert-butyl dicarbonate was carried out as follows: to the product of step A (300 g, 1.01 mol) to a solution of phosphorus oxychloride (POCl3, 1500 mL) was added N,N-dimethylformamide (DMF, 10 mL). The reaction mixture was heated at 90 °C until thin layer chromatography (TLC) analysis (unfolding agent: ethyl acetate/petroleum ether = 1:2) showed complete consumption of the raw material. Excess POCl3 was removed under vacuum and the residue was slowly poured into crushed ice under stirring. The pH of the aqueous solution was adjusted to 8 with solid potassium carbonate (K2CO3) and a solution of di-tert-butyl dicarbonate ((Boc)2O, 235 g, 1.09 mol) and triethylamine (Et3N, 600 mL) in tetrahydrofuran (THF, 1 L) was added. The reaction mixture was stirred at room temperature overnight until TLC analysis (unfolding agent: ethyl acetate/petroleum ether = 1:25) showed complete consumption of the raw material. THF was removed under vacuum and the aqueous solution was extracted with dichloromethane (CH2Cl2, 1L x 3). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate (Na2SO4) and concentrated to give the crude product. The crude product was purified by column chromatography (eluent: ethyl acetate/petroleum ether=1:25) to afford the target product (44 g, 14% yield) as a white solid.1H NMR (400 MHz, CDCl3) δppm: 1.46 (s, 9H), 3.03-3.10 (m, 4H), 3.56 (bs, 4H).

References

[1] Patent: WO2008/117169, 2008, A1. Location in patent: Page/Page column 169

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