* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Method for the synthesis of 2, 2-dimethyl-pvrrolidine hvdrochloride : Lithium aluminium hydride (1M solution in tetrohydrofuran; 120 ml, 120 mmol) was added slowly to a stirred solution of 2, 2-dimethyl-pyrrolidinone (6 g, 53 mmol) in tetrahydrofuran (150 ml). Upon complete addition, the reaction was warmed to reflux, and stirred at reflux under argon for 16 hours. After this time, the reaction was allowed to cool to 0C, before addition of water (2.2 ml), 10% sodium hydroxide solution (2.2 ml) and water (6.6 ml) at 45 minute intervals. The resultant slurry was diluted with diethyl ether (150 mi) and filtered through a pad of celite. The cake was washed with diethyl ether (250 ml) and the filtrate acidified with hydrochloric acid (1 M solution in diethyl ether; 63 ml). The resultant yellow solid was filtered off to afford 2, 2-dimethyl-pyrrolidine hydrochloride (4.8g).
4-Bromo-2-chlorobenzoic acid (1.1 g) and 5-fluoro-2-methoxyphenylboronic acid (0.94 g) were suspended in toluene (20 mL) and ethanol (20 mL). Aqueous 2M sodium carbonate solution (16 mL) and tetrakis(triphenylphosphine) palladium(0) (0.14 g) were added and the reaction was heated at 95 C. for 20 h. The mixture was diluted with water, extracted with diethyl ether (discarded). The aqueous layer was acidified with aqueous 2M hydrochloric acid, extracted with ethyl acetate, dried (MgSO4) and concentrated under reduced pressure to give the sub titled product as a cream solid (1.25 g).MS: APCI(-ve) 279
With triethylamine; In dichloromethane; at 20.0℃;Product distribution / selectivity;
The product from step a) (1.25 g) in DCM (20 mL) was treated with oxalyl chloride (0.44 mL) and a drop of DMF. The mixture was stirred at rt for 1 h and concentrated under reduced pressure to give an oil which was azeotroped with toluene. This acid chloride was dissolved in DCM (10 mL) and treated with the product from b) (0.60 g) followed by triethylamine (0.4 mL) and the reaction was stirred at rt overnight. The organic layer was diluted with DCM and washed with water, dried (MgSO4) and concentrated under reduced pressure to give the sub titled product as a cream solid (0.6 g).MS: APCI(+ve) 362
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 20.0℃; for 2h;
TBTU (110 mg) was added to a solution of the product of example 122b (84 mg), DIPEA (200 mul) and <strong>[623580-01-8]2,2-dimethylpyrrolidine hydrochloride</strong> (62 mul) in NMP (5 ml).After stirring at room temperature for 2 h, the reaction mixture was poured into a sat. aqueous NH4Cl solution and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel in heptane/ethyl acetate [ 1/0 ? 6/4 (v/v)] as eluent.Yield: 76 mg. LC/MS-ESI: [M+H]+ = 449.2; anal. HPLC: R1 = 20.08 min (method 7); hFSHRago (CHO luc) EC50 = 2.0 nM
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
