Related Products of 59-48-3, 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. 59-48-3 name is Indolin-2-one, 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.
A stirred mixture of sodium hydride (60%, 31g, 0.79 mol) in dry xylene (500 mL), under a nitrogen atmosphere, was heated to reflux for 30 min. l,3-Dihydro-indol-2-one 16a (100 g, 0.75 mol) was then slowly added via an addition funnel and stirred at reflux for 1.5 hrs. Dimethyl sulfate (104 g, 0.83 mol) was added drop-wise, whereupon the resulting homogeneous solution was refluxed for an additional 2 hrs. After cooling to room temperature, the reaction mixture was washed with water, dried over Na2SC>4, and concentrated under reduced pressure to afford l-methyl-l,3-dihydro-indol-2-one 16b (74 g, 67.3%). .HNMR (300 MHz, CDC13) 5 7.23-7.31 (m, 2 H), 7.04 (t, J= 7.5 Hz, 1 H), 6.82 (d, J= 7.8 Hz, 1 H), 3.52 (s, 2 H), 3.21 (s, 3 H).[0270] A suspension of NaH (60%, 70 g, 0.48 mol) in THF (300 mL) was stirred for 10 min at 0 C. Then a solution of l-methyl-l,3-dihydro-indol-2-one 16b (70 g, 2.88 mol) in THF (200 mL) was added at 0 C, and the mixture was stirred for 1 h at room temperature. Benzyl-bis-(2-chloro-ethyl)-amine (129 g, 0.48 mol) was added in portions at 0 C. The mixture was stirred overnight at room temperature, and then was poured into ice-water, extracted with EtOAc. The combined organic layers were dried over IS^SO^ and concentrated under reduced pressure. The residue was purified by column on silica gel (P.E./E.A. 2:1) to give compound 16c (24 g, 16.3%). lH NMR (300 MHz, CDCI3) 5 7.25-7.42 (m, 7 H), 7.02-7.07 (m, 1 H), 6.83 (d, J= 7.5, 1 H), 3.68 (s, 2 H), 3.19 (s, 3 H), 2.74-2.99 (m, 2 H), 2.66-2.72 (m, 2 H), 1.93-2.01 (m, 2 H), 1.79-1.85 (m, 2 H).[0271] To a solution of compound 16c (12 g, 39.2 mmol) in MeOH (100 mL) was added Pd(OH)2/C (1.5 g, 20%>) under N2. The suspension was hydrogenated under H2 (50 psi) at room temperature for 4.5 hrs. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure to give the deprotected spiroindolone product 16d (8 g, 94.5%). ]H NMR (400 MHz, DMSO-rf6) 5 7.46 (d, J= 7.2,1 H), 7.23-7.27 (m, 1 H), 6.96-7.03 (m, 2 H), 3.04-3.14 (m, 5 H), 2.83-2.89 (m, 2 H), 1.61-1.67 (m, 2 H), 1.45-1.51 (m, 2 H). MS (ESI) m/z 217.1 [M+H]+ [0272] 1.0 eq of deprotected spiroindolone 16d (22 mg, 0.10 mmol) was dissolved in anhydrous l,2-dichloroethane:l,2-dimethoxyethane (1.0 mL, 1:1 v/v) and treated with 1.5 N-Carbethoxy-4-tropinone (30 mg, 0.15 mmol), followed by titanium tetraisopropoxide (88 /xL, 85 mg, 0.30mmol). The vial was flushed with nitrogen and stirred at room temperature ~70 h. The reactionwas then diluted with methanol (1.0 mL), cooled in an ice-BbO bath and treated with sodiumborohydride (8 mg, 0.20 mmol). After warming to room temperature and stirring for 90 min, thereaction was further diluted with methanol (2.0 mL), quenched with 1.0 N NaOH (500 juL) andstirred vigorously at room temperature for 10 min. The suspension obtained was centrifuged(3K rpm, 10 min) and the supernatant concentrated under reduced pressure. The residueobtained was dissolved in MeOH:acetonitrile (1250 fiL, 1:1 v/v), filtered, and purified byreverse-phase HPLC (2-40% CH3CN/0.1% TFA gradient over 10 min) to yield productcompound no. 149. LC/MS (10-99%) m/z [M+H]+398.2, retention time 1.93 min.
At the same time, in my other blogs, there are other synthetic methods of this type of compound, Indolin-2-one, and friends who are interested can also refer to it.
Reference:
Patent; VERTEX PHARMACEUTICALS, INCORPORATED; WO2006/23852; (2006); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem