阅读说明：本技术 去势治疗相关症状的治疗 (Treatment of symptoms associated with castration therapy ) 是由 C.T.本森 于 2015-09-08 设计创作，主要内容包括：本发明提供了一种治疗去势治疗相关的症状的方法,包括向需要该治疗的患者施用有效量的式I化合物或其药学可接受盐：。(The present invention provides a method of treating a condition associated with castration therapy comprising administering to a patient in need of such treatment an effective amount of a compound of formula I: 。)

1. A process for preparing a compound of formula I:

the method comprises the following steps:

(a) make Zn (CN)₂With a compound of formula II, thereby forming a compound of formula III,

(b) forming a compound of formula I by reacting a compound of formula III with a compound of formula IV

Wherein the step (a) comprises:

(ai) reacting a compound of formula II with Zn (CN)₂、 Zn(OAc)₂Zn and Pd (dppf)₂Cl₂ ·CH₂Cl₂Reacting in DMAC to form a compound of formula III;

(aii) adding water to precipitate and isolate technical grade compound of formula III;

(aiii) dissolving the precipitated isolate of the compound of formula III in a mixture of MTBE and acetone to form a slurry;

(aiv) filtering the slurry to form a filtrate of the compound having formula III;

(av) charcoal, MgSO₄And FLORISIL^TMTreating the filtrate of the compound having formula III; and

(avi) crystallization in heptane to give the compound of formula III, and

wherein said step (b) comprises

(bi) reacting a compound of formula III with 2-chloromethylpyridine hydrochloride and K₂CO₃Reaction in DMAC to give a technical grade compound of formula I;

(bii) isolating technical grade compound of formula I by adding water and filtering; and

(biii) recrystallizing the filtered isolate of the compound of formula I in EtOH three times to produce said compound of formula I.

2. Use of a pharmaceutical composition comprising the compound (S) - (7-cyano-4-pyridin-2-ylmethyl-1, 2,3, 4-tetrahydro-cyclopenta [ b ] indol-2-yl) -carbamic acid isopropyl ester, or a pharmaceutically acceptable salt thereof, obtained by the process of claim 1 for the manufacture of a medicament for treating the symptoms of secondary hypogonadism caused by castration therapy.

3. The use of claim 2, wherein the pharmaceutical composition is in the form of a capsule.

4. Use of the compound (S) - (7-cyano-4-pyridin-2-ylmethyl-1, 2,3, 4-tetrahydro-cyclopenta [ b ] indol-2-yl) -carbamic acid isopropyl ester, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of a condition resulting from secondary hypogonadism caused by castration therapy, wherein said compound is obtained by a process comprising the steps of:

(a) providing a solution of isopropyl (S) - (7-cyano-1, 2,3, 4-tetrahydro-cyclopenta [ b ] indol-2-yl) -carbamate in DMF at about 40 ℃;

(b) adding cesium carbonate to the solution to form a mixture;

(c) adding 2-bromomethylpyridine hydrobromide to the mixture in portions and stirring at 40 ℃ to provide the product in solution;

(d) adding the product in solution to cold water at 0 ℃ to 5 ℃ and stirring to form a solid;

(e) the solid was isolated by filtration and dried to provide the compound (S) - (7-cyano-4-pyridin-2-ylmethyl-1, 2,3, 4-tetrahydro-cyclopenta [ b ] indol-2-yl) -carbamic acid isopropyl ester.

5. The use of claim 4, wherein the method further comprises using CH with silica gel₂Cl₂EtOAc elution purification steps of said compound.

6. The use of claim 4 or claim 5, wherein the method further comprises the step of recrystallizing the compound from ethyl acetate or ethanol.

7. The use of any one of claims 2 and 4-6, wherein the symptom is loss of bone mass, bone strength, muscle mass, or muscle strength.

8. The use of any one of claims 2 and 4-6, wherein the symptoms are loss of libido and hot flashes.