[1,1'-biphenyl]-4-carbonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】28439

【品名】[1,1'-biphenyl]-4-carbonyl chloride

【CA登记号】14002-51-8

【分子式】C₁₃H₉ClO

【分子量】216.66656

【元素组成】C 72.07% H 4.19% Cl 16.36% O 7.38%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(A)

The Diels-Alder reaction of butadiene (VIII) with acrylic acid (IX) gives cyclohexene-4-carboxylic acid (X), which by treatment with I2 and KI in water followed by a treatment with 1,5-diazabicyclo[4.3.0]non-5-ene (XI) in benzene is converted to 3-hydroxycyclohexene-5-carboxylic acid lactone (XII). The opening of (XII) with NaOMe in MeOH yields methyl 3-hydroxycyclohexene-5-carboxylate (XIII) as a mixture of isomers, which by treatment with phenylacetyl chloride (A) affords the corresponding phenylacetate (XIV), which by optical resolution and successive racemization of the residue with mercuric trifluoroacetate yields the active methyl 3-hydroxycyclohexene-5-carboxylate (XIIIa). The treatment of (XIIIa) with biphenylyl-4-carbonyl chloride gives the corresponding ester (XV), which is submitted to hydroxylation with OsO4-sodium chlorate yielding the glycol (XVI). Ring opening of (XVI) with sodium periodate in THF-water affords the dialdehyde (XVII), which is cyclized by treatment with pyrrolidine acetate (B) in benzene giving 5-methoxycarbonyl-3-(biphenylylcarbonyloxy)cyclopentene-1-carboxaldehyde (XVIII). The conjugate addition of (XVIII) with the vinyl cuprate (XIX) in HMPT-THF-ether at -78 C gives rise to 2-[3-(1-ethoxyethoxy)-1-octen-1-yl]-3-(4-biphenylylcarbonyloxy)-5-methyloxycarbonylcyclopentane-1-carboxaldehyde (XX), which is converted into the corresponding ethylene ketal (XXI) in the usual way (C).

参考文献中间体

合成目标

【1】 Trost, B.M.; et al.; An enantioconvergent approach to prostanoids. J Chem Soc Chem Commun 1978, 10, 436-438.
【2】 Castaner, J.; Owen, R.T.; U-46619. Drugs Fut 1980, 5, 9, 453.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	28439	[1,1'-biphenyl]-4-carbonyl chloride	14002-51-8	C₁₃H₉ClO	详情	详情
(B)	39152			C₆H₁₂NO₂	详情	详情
(VIII)	11579	1,3-Butadiene; Butadiene	106-99-0	C₄H₆	详情	详情
(IX)	19139	acrylic acid	79-10-7	C₃H₄O₂	详情	详情
(X)	39146	3-cyclohexene-1-carboxylic acid；Cyclohex-3-ene-1-carboxylic acid	4771-80-6	C₇H₁₀O₂	详情	详情
(XI)	39147	2,3,4,6,7,8-hexahydropyrrolo[1,2-a]pyrimidine	3001-72-7	C₇H₁₂N₂	详情	详情
(XII)	11583	(1R,5R)-6-Oxabicyclo[3.2.1]oct-3-en-7-one		C₇H₈O₂	详情	详情
(XIII)	11584	methyl (1R,5R)-5-hydroxy-3-cyclohexene-1-carboxylate		C₈H₁₂O₃	详情	详情
(XIV)	39148	methyl (1R,5R)-5-[(2-phenylacetyl)oxy]-3-cyclohexene-1-carboxylate		C₁₆H₁₈O₄	详情	详情
(XV)	39149	(1R,5R)-5-(methoxycarbonyl)-2-cyclohexen-1-yl [1,1'-biphenyl]-4-carboxylate		C₂₁H₂₀O₄	详情	详情
(XVI)	39150	(1R,2R,3R,5R)-2,3-dihydroxy-5-(methoxycarbonyl)cyclohexyl [1,1'-biphenyl]-4-carboxylate		C₂₁H₂₂O₆	详情	详情
(XVII)	39151	(1R,3S)-1-formyl-3-(methoxycarbonyl)-5-oxopentyl [1,1'-biphenyl]-4-carboxylate		C₂₁H₂₀O₆	详情	详情
(XVIII)	39153	(1R,4S)-3-formyl-4-(methoxycarbonyl)-2-cyclopenten-1-yl [1,1'-biphenyl]-4-carboxylate		C₂₁H₁₈O₅	详情	详情
(XIX)	39154			C₁₇H₃₀CuO₂	详情	详情
(XX)	39155	(1R,2R,3R,4S)-2-[(E,3S)-3-(1-ethoxyethoxy)-1-octenyl]-3-formyl-4-(methoxycarbonyl)cyclopentyl [1,1'-biphenyl]-4-carboxylate		C₃₃H₄₂O₇	详情	详情
(XXI)	39157	(1R,2R,3R,4S)-3-(1,3-dioxolan-2-yl)-2-[(E,3S)-3-(1-ethoxyethoxy)-1-octenyl]-4-(methoxycarbonyl)cyclopentyl [1,1'-biphenyl]-4-carboxylate		C₃₅H₄₆O₈	详情	详情
(C)	39156	2,2-dimethyl-1,3-dioxolane	2916-31-6	C₅H₁₀O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Condensation of N-Boc-L-phenylalaninal (I) with 4-biphenylcarbonyl chloride (II) and KCN in the presence of N-benzylcinchoninium chloride (NBC) afforded alpha-acyloxynitrile (III) as a 4:1 mixture of (2R,3S) and (2S,3S) isomers. Hydrogenation of (III) in the presence of Raney Nickel and tert-butyl carbazate, followed by crystallization of the major isomer from acetonitrile provided hydrazone (IV). Subsequent reduction of (IV) to hydrazine using NaBH3CN and p-toluenesulfonic acid, with concomitant rearrangement of the biphenylcarbonyl group furnished hydrazide (V), which was reduced to the benzyl hydrazine (VI) by means of either BH3 or DIBAL-H. Deprotection of both Boc groups of (VI) with HCl gave diamino compound (VII). Finally, coupling of N-methoxycarbonyl-L-tert-leucine (IX), (prepared by reaction of tert-leucine (VIII) with methyl chloroformate), with diamine (VII) employing O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyluronium tetra-fluoroborate (TPTU) provided the target bisamide.

参考文献中间体

合成目标

【1】 Fassler, A.; Bold, G.; Capraro, H.-G.; Lang, M. (Novartis AG); Azahexane derivs. as substrate isosters of retroviral asparate proteases. EP 0876336; JP 1999514996; WO 9719055 .
【2】 Fassler, A.; Steiner, H.; Bold, G.; Capraro, H.-G. (Novartis AG); Process for the preparation of hydrazine derivs. useful as intermediates for the preparation of peptide analogues. WO 9746514 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	23452	tert-butyl (1S)-1-benzyl-2-oxoethylcarbamate		C₁₄H₁₉NO₃	详情	详情
(II)	28439	[1,1'-biphenyl]-4-carbonyl chloride	14002-51-8	C₁₃H₉ClO	详情	详情
(III)	28440	(2S)-2-[(tert-butoxycarbonyl)amino]-1-cyano-3-phenylpropyl [1,1'-biphenyl]-4-carboxylate		C₂₈H₂₈N₂O₄	详情	详情
(IV)	28441	(1R,2S)-2-[(tert-butoxycarbonyl)amino]-1-[[(E)-2-(tert-butoxycarbonyl)hydrazono]methyl]-3-phenylpropyl [1,1'-biphenyl]-4-carboxylate		C₃₃H₃₉N₃O₆	详情	详情
(V)	28442	tert-butyl 2-([1,1'-biphenyl]-4-ylcarbonyl)-2-[(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl]-1-hydrazinecarboxylate		C₃₃H₄₁N₃O₆	详情	详情
(VI)	28443	tert-butyl 2-([1,1'-biphenyl]-4-ylmethyl)-2-[(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl]-1-hydrazinecarboxylate		C₃₃H₄₃N₃O₅	详情	详情
(VII)	28444	(2S,3S)-3-amino-1-[1-([1,1'-biphenyl]-4-ylmethyl)hydrazino]-4-phenyl-2-butanol		C₂₃H₂₇N₃O	详情	详情
(VIII)	28445	(2S)-2-amino-3,3-dimethylbutyric acid		C₆H₁₃NO₂	详情	详情
(IX)	23447	(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutyric acid		C₈H₁₅NO₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VIII)

Coupling of 4-aminobutanol (VII) with 4-phenylbenzoyl chloride (VIII) produced hydroxy amide (IX). Further Swern oxidation of the alcohol group of (IX) using oxalyl chloride and DMSO afforded aldehyde (X). Finally, reductive condensation of aldehyde (X) with pyrrolidine (VI) in the presence of NaBH(OAc)3 afforded the title compound.

参考文献中间体

合成目标

【1】 Audinot, V.; Dubuffet, T.; Newman-Tancredi, A.; Cussac, D.; Millan, M.J.; Lavielle, G.; Loutz, A.; Novel benzopyrano[3,4-c]pyrrole derivatives as potent and selective dopamine D3 receptor antagonists. Bioorg Med Chem Lett 1999, 9, 14, 2059.
【2】 Lejeune, F.; Hautefaye, P.; Millan, M.; Dubuffet, T.; Lavielle, G. (ADIR et Cie.); Chromene derivs., process for their preparation and pharmaceutical compsns. containing them. EP 0887350; JP 1999071376; US 6090837 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	33765	(3aR,9bS)-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrole-8-carbonitrile		C₁₂H₁₂N₂O	详情	详情
(VII)	33766	4-amino-1-butanol	13325-10-5	C₄H₁₁NO	详情	详情
(VIII)	28439	[1,1'-biphenyl]-4-carbonyl chloride	14002-51-8	C₁₃H₉ClO	详情	详情
(IX)	33767	N-(4-hydroxybutyl)[1,1'-biphenyl]-4-carboxamide		C₁₇H₁₉NO₂	详情	详情
(X)	33768	N-(4-oxobutyl)[1,1'-biphenyl]-4-carboxamide		C₁₇H₁₇NO₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

Biphenyl-4-carbonyl chloride (I) is esterified with 1,4-butanediol (II) in the presence of pyridine to produce the target 4-hydroxybutyl ester.

参考文献中间体

合成目标

【1】 Greig, I.R.; Ralston, S.H.; Van't Hof, R.J.; Armour, K.J. (University of Aberdeen); Alkane diol derivs. as therapeutic agents for the treatment of bone conditions. WO 0337321 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	28439	[1,1'-biphenyl]-4-carbonyl chloride	14002-51-8	C₁₃H₉ClO	详情	详情
(II)	43160	1,4-butanediol;1,4-Dihydroxybutane;1,4-Butylene glycol;Tetramethylene glycol	110-63-4	C₄H₁₀O₂	详情	详情

Extended Information