SNAP-7941, -Drug Synthesis Database

【结构式】

【药物名称】SNAP-7941

【化学名称】(+)-3-[N-[3-[4-(3-Acetamidophenyl)piperidin-1-yl]propyl]carbamoyl]-4(S)-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid methyl ester hydrochloride

【CA登记号】387825-78-7 (free base)

【分子式】C₃₁H₃₈ClF₂N₅O₆

【分子量】650.12821

【开发单位】Synaptic (Originator)

【药理作用】Antidepressants, Antiobesity Drugs, Anxiolytics, METABOLIC DRUGS, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Treatment of Nutritional Disorders, Melanin-Concentrating Hormone MCH-R1 (SLC-1) Receptor Antagonists

合成路线1 合成路线2 合成路线3

合成路线1

3,4-Difluorobenzaldehyde (I) is condensed with methyl 4-methoxyacetoacetate (II) and urea in the presence of boron trifluoride etherate and copper (I) oxide to produce the dihydropyrimidinone adduct (III). After isolation of the desired enantiomer by means of chiral HPLC, reaction with p-nitrophenyl chloroformate leads to the nitrophenyl carbamate (IV). Then, condensation of (IV) with 3 bromoproylamine (V) furnishes the N-bromopropyl urea derivative (VI).

参考文献中间体

【1】 Gluchowski, C.; Chiu, G.; Marzabadi, M.R.; Nagarathnam, D.; Lagu, B.; Noble, S.; Wetzel, J.; Deleon, J.E. (Synaptic Pharmaceutical Corp.); Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof. EP 1299362; WO 0206245 .

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)	26654	3,4-difluorobenzaldehyde	34036-07-2	C₇H₄F₂O	详情	详情
(II)	26655	methyl 4-methoxy-3-oxobutanoate;Methyl 4-methoxyacetoacetate;Methyl 4-methoxy-3-oxo-butanoate	41051-15-4	C₆H₁₀O₄	详情	详情
(III)	39303	methyl 4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate		C₁₄H₁₄F₂N₂O₄	详情	详情
(IV)	48400	5-methyl 1-(4-nitrophenyl) (6S)-6-(3,4-difluorophenyl)-4-(methoxymethyl)-2-oxo-3,6-dihydro-1,5(2H)-pyrimidinedicarboxylate		C₂₁H₁₇F₂N₃O₈	详情	详情
(V)	25449	3-bromo-1-propanamine; 3-bromopropylamine	18370-81-5	C₃H₈BrN	详情	详情
(VI)	60991	methyl (4S)-3-{[(3-bromopropyl)amino]carbonyl}-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate		C₁₈H₂₀BrF₂N₃O₅	详情	详情

合成路线2

N-Boc-4-Piperidone (VII) is converted into the enol triflate (VIII) upon treatment with N-phenyl trifluoromethanesulfonimide and LDA. Subsequent Suzuki coupling of (VIII) with 3-acetamidophenylboronic acid (IX) yields the 4-aryl tetrahydropyridine (X). Removal of the N-Boc group of (X) under acidic conditions furnishes the deprotected tetrahydropyridine (XI). Optionally, catalytic hydrogenation of (X) gives rise to piperidine (XII), which is then deprotected by acidic treatment to produce (XIII).

参考文献中间体

【1】 Gluchowski, C.; Chiu, G.; Marzabadi, M.R.; Nagarathnam, D.; Lagu, B.; Noble, S.; Wetzel, J.; Deleon, J.E. (Synaptic Pharmaceutical Corp.); Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof. EP 1299362; WO 0206245 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	18620	tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone	79099-07-3	C₁₀H₁₇NO₃	详情	详情
(VIII)	32972	tert-butyl 4-[[(trifluoromethyl)sulfonyl]oxy]-3,6-dihydro-1(2H)-pyridinecarboxylate		C₁₁H₁₆F₃NO₅S	详情	详情
(IX)	60992	3-(acetylamino)phenylboronic acid		C₈H₁₀BNO₃	详情	详情
(X)	60993	tert-butyl 4-[3-(acetylamino)phenyl]-3,6-dihydro-1(2H)-pyridinecarboxylate		C₁₈H₂₄N₂O₃	详情	详情
(XI)	60994	N-[3-(1,2,3,6-tetrahydro-4-pyridinyl)phenyl]acetamide		C₁₃H₁₆N₂O	详情	详情
(XII)	60995	tert-butyl 4-[3-(acetylamino)phenyl]-1-piperidinecarboxylate		C₁₈H₂₆N₂O₃	详情	详情
(XIII)	60996	N-[3-(4-piperidinyl)phenyl]acetamide		C₁₃H₁₈N₂O	详情	详情

合成路线3

Condensation of piperidine (XIII) with the N-bromopropyl derivative (VI) gives rise to the title compound. Alternatively, the title compound can be prepared by condensation of bromide (VI) with tetrahydropyridine (XI) to produce adduct (XIV), which is then hydrogenated over Pd/C.

参考文献中间体

【1】 Gluchowski, C.; Chiu, G.; Marzabadi, M.R.; Nagarathnam, D.; Lagu, B.; Noble, S.; Wetzel, J.; Deleon, J.E. (Synaptic Pharmaceutical Corp.); Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof. EP 1299362; WO 0206245 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	60991	methyl (4S)-3-{[(3-bromopropyl)amino]carbonyl}-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate	C₁₈H₂₀BrF₂N₃O₅	详情	详情
(XI)	60994	N-[3-(1,2,3,6-tetrahydro-4-pyridinyl)phenyl]acetamide	C₁₃H₁₆N₂O	详情	详情
(XIII)	60996	N-[3-(4-piperidinyl)phenyl]acetamide	C₁₃H₁₈N₂O	详情	详情
(XIV)	60997	[1-(cyclopropylmethyl)-2-pyrrolidinyl]methanamine; [1-(cyclopropylmethyl)-2-pyrrolidinyl]methylamine	C₃₁H₃₅F₂N₅O₆	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(2)