Electric Literature of 141452-01-9, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 141452-01-9 name is Methyl indoline-5-carboxylate, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.
(R)-l-(4-cyclopentyl-3-ethyl-l-methyl-2-oxo-l,2,3,4-tetrahydropyrido[2,3-6]pyrazin-6- yl)indoline-5-carboxylic acid (i?)-6-chloro-4-cyclopentyl-3-ethyl-l-methyl-3,4-dihydropyrido[2,3-]pyrazin- 2(lH)-one (20.2 mg, 0.0688 mmol, 1 eq), methyl indoline-5-carboxylate (14.6 mg, 0.0825 mmol, 1.2 eq), Pd2dba3 (3.2 mg, 0.00344 mmol, 5 mol%), XPhos (4.9 mg, 0.0103 mmol, 15 mol%) and K2C03 (38 mg, 0.275 mmol, 4 eq) were dissolved in tBuOH (0.69 mL, 0.1 M) and heated to 100 C for 18 hours. The mixture was filtered through celite, washed with DCM/EtOAc/MeOH and condensed. Purification by column chromatography (ISCO, 4 g silica column, 0-10%MeOH/DCM, 15 minute gradient) gave a mixture of the desired methyl ester and the (inconsequential) ethyl ester, which was used without further purification (29.64 mg). LCMS 434.48 (M+H), 449.47 (ethyl ester M+H). The resulting material was dissolved in THF (0.34 mL) and water (0.17 mL). LiOH (2.4 mg) was added and the mixture was stirred at room temperature. Due to poor solubility and sluggish conversion, an additional 2.4 mg LiOH, 0.17 mL water and 0.17 mL MeOH were added. After 2 days, the mixture was diluted with MeOH and purified by preparative HPLC to give a dark brown oil (16.78 mg, 0.0399 mmol, 59% over 2 steps. 1H NMR (400 MHz, Chloroform-;/) delta 8.10 (d, J= 8.6 Hz, 1H), 7.83 (dd, J= 8.6, 1.7 Hz, 1H), 7.79 – 7.74 (m, 1H), 7.16 – 7.1 1 (m, 1H), 6.21 (d, J= 8.4 Hz, 1H), 4.62 – 4.54 (m, 1H), 4.13 – 4.00 (m, 3H), 3.31 – 3.30 (m, 3H), 3.20 (t, J = 8.7 Hz, 2H), 2.14 – 2.04 (m, 2H), 1.80 – 1.54 (m, 8H), 0.86 (td, J = 7.6, 2.8 Hz, 3H). LCMS 421.51 (M+H).
At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl indoline-5-carboxylate, and friends who are interested can also refer to it.
Reference:
Patent; DANA-FARBER CANCER INSTITUTE, INC.; BRADNER, James, E.; GRAY, Nathanael; QI, Jun; MCKEOWN, Michael, R.; BUCKLEY, Dennis; WO2015/117055; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem