Z-D-ASP(OTBU)-OH H2O

White powder

In a 5L four-neck flask, 80 g of (R) -2- (benzyloxycarbonyl) -4-tert-butoxy-4-oxobutanoic acid (compound 1) was dissolved in 800 mL of tetrahydrofuran, and the temperature was reduced to -10. , 26.1 g of N-methylmorpholine were added, followed by dropwise 34 g of isobutyl chloroformate. After dripping, stir at -10 for 30min. After filtration, the filter cake was rinsed with 200 mL of tetrahydrofuran. The filtrate was transferred to a 5L reaction flask, the temperature was lowered to -30 C, 17.9 g of sodium borohydride was added, and then 500 mL of methanol was added to react for 1 h. TLC analysis of the raw materials was complete. Add 500 mL of water dropwise, adjust the pH to 6-7 with acetic acid, add 1 L of water, extract 3 times with ethyl acetate (3 × 800 mL), wash the organic phase with dilute hydrochloric acid, and then wash with brine. It was dried over sodium sulfate, concentrated to dryness, and passed through the column to obtain 65 g of tert-butyl (R) -3- (benzyloxycarbonyl) -4-hydroxybutyrate (Compound 2). The yield was 92.3%N-[(Benzyloxy)carbonyl]-D-alpha-asparagyl-N1-{(2S)-4-[{(1R)-1-[1-benzyl-4-(2, 5-difluorophenyl)-1H-pyrrol-2-yl]-2, 2-dimethylpropyl}(glycoloyl)amino]-1-[(2-{[(2, 5-dioxo-2, 5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethyl)amino]-1-oxobutan-2-yl}-L-aspartamide The title compound was prepared from compound C116 first by coupling to To a solution of Z-D-Asp(Ot-Bu)-OH (2.0 g, 6.2 mmol) in acetone (10 mL) was added K2CO3 (1.2 g, 8.7 mmol) followed by methyl iodide (0.39 mL, 6.2 mmol). The reaction mixture was stirred at 23C for 2.5 h over which time a thick white precipitate had formed. More acetone was added (20 mL), and the mixture was stirred at 23C for an additional 16 h. Additional methyl iodide was then added (0.20 mL, 3.1 mmol), and the mixture was stirred for an additional 24 h. The mixture was concentrated in vacuo. The crude residue was taken up in EtOAc (100 mL), and washed with sat. NaHCO3 (aq) (1X100 mL) and brine (1X50 mL). The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo to provide 2.0 g (96%) of (R)-4-tert-butyl 1-methyl 2- (((benzyloxy)carbonyl)amino)succinate.1H NMR (400 MHz, CDCl3): d ppm 8.71 (m, 1H), 8.56 (dd, 1H), 8.54 (d, 1H), 5.61 (t, 1H), 4.63 (d, 2H); LCMS (Method A) tR= 1.28 min, m/z 360.3 (M+Na)+.

Z-D-Asp(OtBu)-OH is an aspartic acid derivative[1].

Molecular Weight:323.34
XLogP3:1.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:9
Exact Mass:323.13688739
Monoisotopic Mass:323.13688739
Topological Polar Surface Area:102
Heavy Atom Count:23
Complexity:423
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes