Hexanedioyl dichloride; Adipoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】52933

【品名】Hexanedioyl dichloride; Adipoyl chloride

【CA登记号】

【分子式】C₆H₈Cl₂O₂

【分子量】183.03372

【元素组成】C 39.37% H 4.41% Cl 38.74% O 17.48%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The Friedel-Crafts condensation of 2-(2'-methoxybiphenyl-3-yl)acetic acid ethyl ester (I) with adipoyl dichloride (II) by means of AlCl3 gives the adduct (III), which is treated with BBr3 to cleave the methoxy groups and yield the diphenolic compound (IV). The condensation of (IV) with alpha-D-mannose pentaacetate (V) by means of BF3/Et2O affords the bis glycoside (VI), which is hydrolyzed with aq. LiOH aq. or NaOH to provide the dicarboxylic acid (VII). Finally, both ketonic groups of (VII) are reduced with LiOH and N2H4, or with Et3SiH, TFA and BF3/Et2O, or with H2, Pd(OH)2 and BBr3, to furnish the target bis mannopyranoside.

参考文献中间体

合成目标

【1】 Dupré, B.; Beck, P.J.; Vanderslice, P.; Hu, X.; Scott, I.L.; Kassir, J.M.; McAbee, K.L.; Bui, H.; Dixon, R.A.F.; Kogan, T.P.; Novel synthetic inhibitors of selectin-mediated cell adhesion: Synthesis of 1, 6-bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D-mannopyranosyloxy)phenyl]hexane (TBC1269). J Med Chem 1998, 41, 7, 1099.

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)	54316	ethyl 2-(2'-methoxy[1,1'-biphenyl]-3-yl)acetate	n/a	C₁₇H₁₈O₃	详情	详情
(II)	52933	Hexanedioyl dichloride; Adipoyl chloride		C₆H₈Cl₂O₂	详情	详情
(III)	54317	ethyl 2-(5'-{6-[3'-(2-ethoxy-2-oxoethyl)-6-methoxy[1,1'-biphenyl]-3-yl]-6-oxohexanoyl}-2'-methoxy[1,1'-biphenyl]-3-yl)acetate	n/a	C₄₀H₄₂O₈	详情	详情
(IV)	54318	ethyl 2-(5'-{6-[3'-(2-ethoxy-2-oxoethyl)-6-hydroxy[1,1'-biphenyl]-3-yl]-6-oxohexanoyl}-2'-hydroxy[1,1'-biphenyl]-3-yl)acetate	n/a	C₃₈H₃₈O₈	详情	详情
(V)	54319	[(2R,3R,4S,5S,6R)-3,4,5,6-tetrakis(acetyloxy)tetrahydro-2H-pyran-2-yl]methyl acetate	n/a	C₁₆H₂₂O₁₁	详情	详情
(VI)	54320	ethyl 2-[5'-{6-[3'-(2-ethoxy-2-oxoethyl)-6-({(2R,3S,4S,5R,6R)-3,4,5-tris(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)[1,1'-biphenyl]-3-yl]-6-oxohexanoyl}-2'-({(3S,4S,5R,6R)-3,4,5-tris(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)[1,1'-biphenyl]-3-yl]acetate	n/a	C₆₆H₇₄O₂₆	详情	详情
(VII)	54321	2-(5'-[6-(3'-(2-hydroxy-2-oxoethyl)-6-{[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}[1,1'-biphenyl]-3-yl)-6-oxohexanoyl]-2'-{[(3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}[1,1'-biphenyl]-3-yl)acetic acid	n/a	C₄₆H₅₀O₁₈	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The Friedel-Crafts condensation of 2-(2'-methoxybiphenyl-3-yl)acetic acid (VIII) with adipoyl dichloride (II) by means of AlCl3 in dichloromethane gives the adduct (IX), which is submitted to reduction of both carbonyl groups by means of LiOH and N2H4, or with Et3SiH, TFA and BF3/Et2O, or with H2, Pd(OH)2 and BBr3, to yield the hexane-1,6-diyl derivative (X). The cleavage of the methoxy groups of (X) by means of BBr3 in dichloromethane affords the bis phenolic compound (XI), which is condensed with alpha-D-mannose pentaacetate (V) by means of BF3/Et2O in dichloroethane to provide the bis glycoside (XII). Finally, this compound is hydrolyzed with LiOH in water to furnish the target bis mannopyranoside.

参考文献中间体

合成目标

【1】 Mukherjee, A.K.; Dasgupta, F.; Novel synthetic inhibitors of selection-mediated cell adhesion: Synthesis of 1,6-bis [3-(3-carboxymethylphenyl)-4-(O-alpha-D-mannopyranosyl)phenyl]hexane (TBC 1269). Chemtracts - Org Chem 2000, 13, 9, 1431.
【2】 Kogan, T.P.; Dupre, B.; Scott, I.L.; Bui, H.; Wheeler, K.L.; Keller, K.M.; Kassir, J.M. (Texas Biotechnology Corp.); Di- and trivalent small molecule selectin inhibitors. JP 1999508885; WO 9701335 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	52933	Hexanedioyl dichloride; Adipoyl chloride		C₆H₈Cl₂O₂	详情	详情
(V)	54319	[(2R,3R,4S,5S,6R)-3,4,5,6-tetrakis(acetyloxy)tetrahydro-2H-pyran-2-yl]methyl acetate	n/a	C₁₆H₂₂O₁₁	详情	详情
(VIII)	54322	2-(2'-methoxy[1,1'-biphenyl]-3-yl)acetic acid	187269-42-7	C₁₅H₁₄O₃	详情	详情
(IX)	54323	2-(5'-{6-[3'-(2-hydroxy-2-oxoethyl)-6-methoxy[1,1'-biphenyl]-3-yl]-6-oxohexanoyl}-2'-methoxy[1,1'-biphenyl]-3-yl)acetic acid	n/a	C₃₆H₃₄O₈	详情	详情
(X)	54324	2-(5'-{6-[3'-(2-hydroxy-2-oxoethyl)-6-methoxy[1,1'-biphenyl]-3-yl]hexyl}-2'-methoxy[1,1'-biphenyl]-3-yl)acetic acid	n/a	C₃₆H₃₈O₆	详情	详情
(XI)	54325	2-(2'-hydroxy-5'-{6-[6-hydroxy-3'-(2-hydroxy-2-oxoethyl)[1,1'-biphenyl]-3-yl]hexyl}[1,1'-biphenyl]-3-yl)acetic acid	n/a	C₃₄H₃₄O₆	详情	详情
(XII)	54326	2-[5'-{6-[3'-(2-hydroxy-2-oxoethyl)-6-({(2R,3S,4S,5R,6R)-3,4,5-tris(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)[1,1'-biphenyl]-3-yl]hexyl}-2'-({(3S,4S,5R,6R)-3,4,5-tris(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)[1,1'-biphenyl]-3-yl]acetic acid	n/a	C₆₂H₇₀O₂₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The synthesis of Ro-63-8695 can be performed by first coupling of D-proline-benzylester hydrochloride (I) with adipoyl chloride (II) by means of Et3N in dichloromethane to furnish benzyl 1-[6-[2(R)-carboxy-1-pyrrolidinyl]-6-oxohexanoyl]pyrrolidine-2(R)-carboxylate (III), which is finally hydrogenated over Pd/C in MeOH.

参考文献中间体

合成目标

【1】 Jacob-Roetne, R.; Hertel, C.; Hoffmann, T.; Norcross, R.D. (F. Hoffmann-La Roche AG); D-Proline derivs.. CA 2252163; EP 0915088; JP 1999209343; US 6262089 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	52935	Benzyl (2R)-2-pyrrolidinecarboxylate; D-Proline-benzylester hydrochloride	C₁₂H₁₅NO₂	详情	详情
(II)	52933	Hexanedioyl dichloride; Adipoyl chloride	C₆H₈Cl₂O₂	详情	详情
(III)	52934	Benzyl (2R)-1-(6-{(2R)-2-[(benzyloxy)carbonyl]pyrrolidinyl}-6-oxohexanoyl)-2-pyrrolidinecarboxylate; Benzyl 1-[6-[2(R)-carboxy-1-pyrrolidinyl]-6-oxohexanoyl]pyrrolidine-2(R)-carboxylate	C₃₀H₃₆N₂O₆	详情	详情

Extended Information