CarbaMic acid, N-[(1S)-3-Methyl-1-[[(2R)-2-Methyl-2-oxiranyl]carbonyl]butyl]-, 1,1-diMethylethyl ester Chemical Properties

Boiling point:

369.8±37.0 °C(Predicted)

Density 

1.061±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

pka

11.08±0.46(Predicted)

Appearance

White to yellow <39°C Solid,>41°C Liquid

InChI

InChI=1S/C14H25NO4/c1-9(2)7-10(11(16)14(6)8-18-14)15-12(17)19-13(3,4)5/h9-10H,7-8H2,1-6H3,(H,15,17)/t10-,14+/m0/s1

InChIKey

DDMPMIMTLBGEHT-IINYFYTJSA-N

SMILES

C(OC(C)(C)C)(=O)N[C@H](C([C@@]1(C)CO1)=O)CC(C)C

CarbaMic acid, N-[(1S)-3-Methyl-1-[[(2R)-2-Methyl-2-oxiranyl]carbonyl]butyl]-, 1,1-diMethylethyl ester Usage And Synthesis

Uses

tert-Butyl ((S)-4-Methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)carbamate is an intermediate of Carfilzomib (C183460) which is a second-generation proteasome inhibitor that is used as a treatment in relapsed and refractory multiple myeloma.

Synthesis

The general procedure for the synthesis of tert-butyl N-[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-2-pentyl]carbamate from tert-butyl (S)-(2,6-dimethyl-3-oxohept-1-en-4-yl)carbamate is as follows: tert-butyl (S)-(2,6-dimethyl-3-oxohept-1-en-4-yl) tert-butyl carbamate (102 g, 0.4 mol) and asymmetric chiral catalyst (R)-La-BINOL (3.24 g, 2 mol%) were added to a 1 L reaction flask, followed by triphenylphosphine (14.8 g, 20 mol%) and 500 mL of toluene and stirred at room temperature. Subsequently, tert-butanol (108 g, 1.2 mol) was added slowly and dropwise. After 0.5 h of reaction, the progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was filtered and the filtrate was collected. The filtrate was quenched with 300 mL of saturated sodium sulfite solution. Tetrahydrofuran was removed by evaporation under reduced pressure and then extracted with 400 mL of ethyl acetate. The organic phase was washed sequentially with 100 mL of water and 100 mL of saturated saline, dried over anhydrous sodium sulfite, and concentrated under reduced pressure to give 92 g of a pale yellow oil, the target product N-[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-2-pentyl]carbamic acid tert-butyl ester in a yield of 85.0% with an ee value of 93%.

References

[1] Patent: CN104672179, 2017, B. Location in patent: Paragraph 0009; 0024; 0025; 0027-0043
[2] Patent: WO2018/100050, 2018, A1. Location in patent: Page/Page column 15; 16; 17; 18
[3] ChemBioChem, 2012, vol. 13, # 6, p. 810 - 817
[4] Patent: WO2013/9923, 2013, A1. Location in patent: Sheet 4; 5
[5] Bioorganic and Medicinal Chemistry, 2018,

CarbaMic acid, N-[(1S)-3-Methyl-1-[[(2R)-2-Methyl-2-oxiranyl]carbonyl]butyl]-, 1,1-diMethylethyl ester(247068-82-2)Related Product Information

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