2-Bromo-1-cyclopropyl-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】12436

【品名】2-Bromo-1-cyclopropyl-1-ethanone

【CA登记号】69267-75-0

【分子式】C₅H₇BrO

【分子量】163.01398

【元素组成】C 36.84% H 4.33% Br 49.02% O 9.81%

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：(XII)

The treatment with NaHCO3 of the corresponding mixture of the 6(R)- and 6(S)-SO2-aldehydic adducts (VIII) gives a mixture of the 20(R) and 20(S) epimeric aldehydes (IX). The Wittig condensation of the aldehyde mixture (IX) with cyclopropylcarbonylmethylenetriphenylphosphorane (X) [prepared from acetylcyclopropane (XI) by bromination to bromoacetylcyclopropane (XII), reaction with triphenylphosphine (XIII) to the phosphonium salt (XIV) and treatment with NaOH] in DMSO at 105 C, followed by chromatographic separation yields the epimeric 20(R)-enone (XV). The reduction of (XV) with NaBH4 and CeCl3 in THF-methanol, followed by chromatographic purification affords the epimeric 3'(R)-allylic alcohol (XVI), which is isomerized by irradiation with UV-light from a TQ 718Z2 Hanau lamp in toluene in the presence of anthracene to give the corresponding 5(Z)-derivative (XVII). Finally, this compound is deprotected by a treatment with tetrabutylammonium fluoride in THF at 60 C.

参考文献中间体

合成目标

【1】 Calverley, M.J.; Synthesis of MC 903, a biologically active vitamin D metabolite analogue. Tetrahedron 1987, 43, 20, 4609-19.
【2】 Binderup, E.; CALCIPOTRIOL. Drugs Fut 1990, 15, 1, 15.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	12432	(2S)-2-[(1R,3aR,7aR)-4-[(E)-((4S,6R)-4,6-bis[[tert-Butyl(dimethyl)silyl]oxy]-2,2-dioxooctahydro-1H-2-benzothiophen-1-yl)methylidene]-7a-methyloctahydro-1H-inden-1-yl]propanal		C₃₄H₆₂O₅SSi₂	详情	详情
(IX)	12433	2-[(1R,3aS,7aR)-4-[(E)-2-((3S,5R)-3,5-bis[[tert-Butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]propanal		C₃₄H₆₀O₃Si₂	详情	详情
(X)	12434	1-cyclopropyl-2-(triphenylphosphoranylidene)-1-ethanone		C₂₃H₂₁OP	详情	详情
(XI)	12435	Acetylcyclopropane; 1-Cyclopropyl-1-ethanone; Cyclopropylmethylketone	765-43-5	C₅H₈O	详情	详情
(XII)	12436	2-Bromo-1-cyclopropyl-1-ethanone	69267-75-0	C₅H₇BrO	详情	详情
(XIII)	12437	Triphenylphosphine; Triphenyl phosphine	603-35-0	C₁₈H₁₅P	详情	详情
(XIV)	12438	(2-Cyclopropyl-2-oxoethyl)(triphenyl)phosphonium bromide	112849-15-7	C₂₃H₂₂BrOP	详情	详情
(XV)	12439	(E,4R)-4-[(1R,3aR,7aR)-4-[(E)-2-((3S,5R)-3,5-Bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-cyclopropyl-2-penten-1-one		C₃₉H₆₆O₃Si₂	详情	详情
(XVI)	12440	(1S,2E,4R)-4-[(1R,3aR,7aR)-4-[(E)-2-((3S,5R)-3,5-Bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-cyclopropyl-2-penten-1-ol		C₃₉H₆₈O₃Si₂	详情	详情
(XVII)	12441	(1S,2E,4R)-4-[(1R,3aR,7aR)-4-[(E)-2-((3S,5R)-3,5-Bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-cyclopropyl-2-penten-1-ol		C₃₉H₆₈O₃Si₂	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 reaction of N1-amidino-N3-phenylthiourea (I) with 2-bromo-1-cyclopropylethanone (II) in ethanol/acetone gives the N1-amidino-S-(2-cyclopropyl-2-oxoethyl)-N3-phenylisothiourea (III), which without isolation is cyclized to the target aminothiazole by means of TEA.

参考文献中间体

合成目标

【1】 Sorensen, A.R.; Engelhardt, S.; Kurtzhals, P.; Urso, B.; Bowler, A.N.; 2,4-Diaminothiazoles: A novel class of glycogen synthase kinase-3 (GSK-3) inhibitors. 11th RSC-SCI Med Chem Symp (Sept 9 2001, Cambridge) 2001, Abst P20.
【2】 Olesen, P.H.; Kurtzhals, P.; Bowler, A.N.; Soerensen, A.R.; Worsaae, H.; Hansen, B.F. (Novo Nordisk A/S); 2,4-Diaminothiazole derivs.. WO 0156567 .

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)	53527	1-Phenyl-3-guanylthiourea	15989-47-6	C₈H₁₀N₄S	详情	详情
(II)	12436	2-Bromo-1-cyclopropyl-1-ethanone	69267-75-0	C₅H₇BrO	详情	详情
(III)	53528	N-{(Z)-anilino[(2-cyclopropyl-2-oxoethyl)sulfanyl]methylidene}guanidine	n/a	C₁₃H₁₆N₄OS	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The reaction of aniline (I) with di(2-pyridyl)thione (DPT) gives the corresponding isothiocyanate (II), which is condensed with cyanamide (III) and 2-bromo-1-cyclopropylethanone (IV) (obtained by bromination of acetylcyclopropane (V)) by means of NaOMe to yield the adduct (VI). This compound, without isolation, cyclizes to the target thiazole.

参考文献中间体

合成目标

【1】 Sorensen, A.R.; Engelhardt, S.; Kurtzhals, P.; Urso, B.; Bowler, A.N.; 2,4-Diaminothiazoles: A novel class of glycogen synthase kinase-3 (GSK-3) inhibitors. 11th RSC-SCI Med Chem Symp (Sept 9 2001, Cambridge) 2001, Abst P20.
【2】 Olesen, P.H.; Kurtzhals, P.; Bowler, A.N.; Soerensen, A.R.; Worsaae, H.; Hansen, B.F. (Novo Nordisk A/S); 2,4-Diaminothiazole derivs.. WO 0156567 .

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)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情
(II)	22146	1-isothiocyanatobenzene; phenyl isothiocyanate	103-72-0	C₇H₅NS	详情	详情
(III)	19648	Cyanamide	420-04-2	CH₂N₂	详情	详情
(IV)	12436	2-Bromo-1-cyclopropyl-1-ethanone	69267-75-0	C₅H₇BrO	详情	详情
(V)	12435	Acetylcyclopropane; 1-Cyclopropyl-1-ethanone; Cyclopropylmethylketone	765-43-5	C₅H₈O	详情	详情
(VI)	53529	(Z)-3-anilino-3-[(2-cyclopropyl-2-oxoethyl)sulfanyl]-2-propenenitrile	n/a	C₁₄H₁₄N₂OS	详情	详情

Extended Information