Preparing lenacapavir intermediate for preparing lenacapavir, involves treating bicyclo[3.1.0]hexan-2-one compound with protecting group, oxidizing hydroxy-substituted dioxaspiro compound, combining oxo-substituted dioxaspiro compound with trifluoroacetylating agent and hydrazine, and fluorinating
	PADALA B; DASARI S; MITTAPELLY N; YERVA E; RAVI V K; JAYACHANDRA S
	2023-08-24
专利权人	MYLAN LAB LTD (MYLA-C)
申请日期	2023-08-24
专利号	IN202341056823-A
成果简介	NOVELTY - Preparing lenacapavir intermediate (I) involves: (a) treating bicyclo[3.1.0]hexan-2-one compound (IX) with a ketal protecting group to obtain dioxaspiro compound (VIII); (b) oxidizing compound (VIII) to obtain hydroxy-substituted dioxaspiro compound (VII); (c) oxidizing compound (VII) to obtain oxo-substituted dioxaspiro compound (VI); (d) combining compound (VI) with trifluoroacetylating agent and lithium base to obtain trifluoromethyl-substituted dioxaspiro compound (V); (e) combining compound (V) with a hydrazine compound (X) to obtain dioxaspiro compound (IV); (f) deprotecting compound (IV) to obtain 3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole compound (III); (g) fluorinating compound (III) to obtain fluorinated 3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole compound (II); and (h) converting compound (II) to lenacapavir intermediate (I). USE - Method for preparing lenacapavir intermediate for preparing lenacapavir. ADVANTAGE - None given. DETAILED DESCRIPTION - Preparing lenacapavir intermediate of formula (I) involves: (a) treating bicyclo[3.1.0]hexan-2-one compound of formula (IX) with a ketal protecting group to obtain dioxaspiro compound of formula (VIII); (b) oxidizing compound (VIII) to obtain hydroxy-substituted dioxaspiro compound of formula (VII); (c) oxidizing compound (VII) to obtain oxo-substituted dioxaspiro compound of formula (VI); (d) combining compound (VI) with trifluoroacetylating agent and lithium base to obtain trifluoromethyl-substituted dioxaspiro compound of formula (V); (e) combining compound (V) with a hydrazine compound of formula (X) to obtain dioxaspiro compound of formula (IV); (f) deprotecting the compound (IV) to obtain 3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole compound of formula (III); (g) fluorinating compound (III) to obtain fluorinated 3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole compound of formula (II); and (h) converting compound (II) to 2-(5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetic acid compound i.e. lenacapavir intermediate (I). R1,R2=H, alkyl, or aryl alkyl; n=1-5; R=-COOR3, -CN, -CONH2; or R3=alkyl, or aryl alkyl. An INDEPENDENT CLAIM is included for a method for preparing amino-protected 1-(3,6-dibromopyridin-2-yl)-2-(3,5-difluorophenyl) compound of formula (XI), which comprises: (i) providing a racemic mixture of 1-(3,6-dibromopyridin-2-yl)-2-(3,5-difluorophenyl) compound of formula (XIV) in an organic solvent; (ii) adding L-phenylalanine p-toluene sulfonamide or di-p-toluoyl-Ltartaric acid to the reaction mixture obtained in step (a); (iii) isolating chiral salt of formula (XIII); (iv) converting compound of formula (XIII) to deprotected amine compound formula (XII); and (v) protecting the compound (XII) to obtain compound (XI). X=L-phenylalanine p-toluenesulfonamide, or di-p-toluoyl-Ltartaric acid; and P1=amine protecting group such as carbobenzyloxy (CbZ), tert-butyloxycarbonyl (Boc), benzoyl (BZ), benzyl (Bn), tosyl (Ts), or p-methoxybenzyl (PMB).
IPC 分类号	A61K-031/4439 ; A61K-009/00 ; A61P-031/18 ; C07D-401/14
国家	印度
专业领域	医药卫生
语种	英语
成果类型	专利
文献类型	科技成果
条目标识符	http://119.78.100.226:8889/handle/3KE4DYBR/20702
专题	中国科学院新疆生态与地理研究所
作者单位	MYLAN LAB LTD (MYLA-C)
推荐引用方式 GB/T 7714	PADALA B,DASARI S,MITTAPELLY N,et al. Preparing lenacapavir intermediate for preparing lenacapavir, involves treating bicyclo[3.1.0]hexan-2-one compound with protecting group, oxidizing hydroxy-substituted dioxaspiro compound, combining oxo-substituted dioxaspiro compound with trifluoroacetylating agent and hydrazine, and fluorinating. IN202341056823-A[P]. 2023.

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