208122-09-2

Upstream product

• 654-70-6 4-amino-2-trifluoromethylbenzonitrile 
• 1259327-69-9 2-bromo-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-methylpropanamide 
• 30992-29-1 Boc-Aib-OH 
• 94744-50-0 N-[(9H-fluoren-9-ylmethoxy)carbonyl]-α-aminoisobutyric acid 

Downstream Products

• 143782-20-1 4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile 
• 154992-24-2 4-[3-(4-hydroxybutyl)-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 
• 1289942-55-7 4-[1-(4-cyano-3-trifluoromethyl-phenylcarbamoyl)-1-methyl-ethylamino]-2-fluoro-N-methyl-benzamide 
• 1802242-43-8 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorobenzoic acid methyl ester 

Relevant academic research and scientific papers

Alternative synthesis of the anti-baldness compound RU58841

RU58841 is active against baldness and is commercially available. The previously reported synthesis uses phosgene, three discrete inert atmosphere steps and three steps that require flash chromatography. Our synthesis uses no phosgene, only one inert atmosphere step and does not require flash chromatography. This is achieved by stepwise construction of the hydantoin moiety around the amino group of 3-trifluoromethyl-4-cyanoaniline and ring closure to give a 2-nitropropane leaving group. On a small scale we achieved an overall yield of 33%.

One-pot method for preparing 2-amino-N-(3-trifluoromethyl-4-cyanophenyl)-2-methylpropionamide compound and salts of compound

The invention discloses a one-pot method for preparing 2-amino-N-(3-trifluoromethyl-4-cyanophenyl)-2-methylpropionamide compound represented by a formula (IV) shown in the description and salts of thecompound. The compound represented by the formula (IV) and the salts of the compound are important intermediates for preparing anti-prostate cancer drug enzalutamide. The method comprises the following steps: performing a condensation reaction by using a compound represented by a formula (I) shown in the description and a compound having an amino protecting group PG represented by a formula (II)shown in the description as raw materials to produce a compound represented by a formula (III) shown in the description; and directly performing a protecting group PG removing reaction without purification on the compound represented by the formula (III) to form the compound represented by the formula (IV) or the salts of the compound represented by the formula (IV). The method provided by the invention is safe and environmentally friendly, purification operation is omitted, the operation is simple, the yield of the two steps is high, the intermediate is easy to store, and the method has larger production and usage value.

Preparation method of enzalutamide of formula (VIII)

The invention discloses a preparation method of enzalutamide of formula (VIII). The method comprises the following steps: carrying out a condensation reaction on a compound of formula (I) and an aminoprotecting group PG-containing compound of formula (II) to produce a compound of formula (III); carrying out a protecting group PG removal reaction on the compound of formula (III) to form a compoundof formula (IV); carrying out a coupling reaction on the compound of formula (IV) and a compound of formula (V) at 25-160 DEG C to form a compound of formula (VI); and converting the compound of formula(VI-a) into a compound of formula (VII) when W is a C1-8 alkoxy group, and converting the compound of formula (VI-b) into into the compound of the formula (VIII) when the W is a methylamino group.The method has the advantages of high yield, omitting of the production of an intermediate isothiocyanate with poor stability, mild reaction conditions, simplicity in operation, and cheap and easily available reagents, is suitable for small-scale preparation in the laboratory, and is also suitable for large-scale industrial production.

NON-STEROIDAL ANTIANDROGENS AND SELECTIVE ANDROGEN RECEPTOR MODULATORS WITH A PYRIDYL MOIETY

Compounds having the structure or their salts: are used to treat or reduce the likelihood of acquiring androgen-dependent diseases, such as prostate cancer, benign prostatic hyperplasia, polycystic ovarian syndrome, acne, hirsutism, seborrhea, androgenic alopecia, male baldness, muscle atrophy and weakness, sarcopenia, male hypogonadism, erectile dysfunction, female sexual dysfunction and osteoporosis. They can be formulated together with pharmaceutically acceptable diluent or carrier or otherwise made into any pharmaceutical dosage form. Combinations with other active pharmaceutical agents are also disclosed.