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【结 构 式】

【分子编号】53047

【品名】5-[(1-methyl-1H-pyrazol-4-yl)methyl]-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone

【CA登记号】n/a

【 分 子 式 】C9H10N4OS

【 分 子 量 】222.27076

【元素组成】C 48.63% H 4.53% N 25.21% O 7.2% S 14.43%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VII)

The Knoevenagel condensation of 1-methylpyrazole-4-carboxaldehyde (I) with malonic acid afforded the pyrazolylacrylic acid (II), which was further esterified with methanol and sulfuric acid, yielding ester (III). Catalytic hydrogenation of the unsaturated ester (III) in the presence of Pd/C gave the pyrazolylpropionate (IV). Claisen condensation of ester (IV) with methyl formate by using potassium tert-butoxide produced the (hydroxymethylene)propionate (V), which was subsequently cyclized with thiourea (VI) to furnish the thiouracil derivative (VII). Alkylation of (VII) with 4-fluorobenzyl chloride (VIII) gave rise to the thioether (IX). Regioselective alkylation of pyrimidine (IX) with tert-butyl iodoacetate produced the pyrimidinylacetate (X). The tert-butyl ester of (X) was then cleaved with trifluoroacetic acid yielding carboxylic acid (XI).

1 Smith, S.A.; Inhibition of lipoprotein-associated phospholipase A2 - A novel approach for the treatment of atherosclerosis. 11th RSC-SCI Med Chem Symp (Sept 9 2001, Cambridge) 2001, Abst .
2 Ife, R.J.; Leach, C.A.; Smith, S.A.; Pinto, I.L.; Hickey, D.M.B.; Fenwick, A.E. (GlaxoSmithKline plc); Pyrimidinone cpds.. EP 1175408; WO 0066567 .
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) 53042 1-methyl-1H-pyrazole-4-carbaldehyde n/a C5H6N2O 详情 详情
(II) 53043 (E)-3-(1-methyl-1H-pyrazol-4-yl)-2-propenoic acid n/a C7H8N2O2 详情 详情
(III) 53044 methyl (E)-3-(1-methyl-1H-pyrazol-4-yl)-2-propenoate n/a C8H10N2O2 详情 详情
(IV) 53045 methyl 3-(1-methyl-1H-pyrazol-4-yl)propanoate n/a C8H12N2O2 详情 详情
(V) 53046 methyl (Z)-3-hydroxy-2-[(1-methyl-1H-pyrazol-4-yl)methyl]-2-propenoate n/a C9H12N2O3 详情 详情
(VI) 10180 Thiourea 62-56-6 CH4N2S 详情 详情
(VII) 53047 5-[(1-methyl-1H-pyrazol-4-yl)methyl]-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone n/a C9H10N4OS 详情 详情
(VIII) 12354 4-Fluorobenzyl chloride; 1-(Chloromethyl)-4-fluorobenzene 352-11-4 C7H6ClF 详情 详情
(IX) 53048 2-[(4-fluorobenzyl)sulfanyl]-5-[(1-methyl-1H-pyrazol-4-yl)methyl]-4(1H)-pyrimidinone n/a C16H15FN4OS 详情 详情
(X) 53049 tert-butyl 2-[2-[(4-fluorobenzyl)sulfanyl]-5-[(1-methyl-1H-pyrazol-4-yl)methyl]-4-oxo-1(4H)-pyrimidinyl]acetate n/a C22H25FN4O3S 详情 详情
(XI) 53050 2-[2-[(4-fluorobenzyl)sulfanyl]-5-[(1-methyl-1H-pyrazol-4-yl)methyl]-4-oxo-1(4H)-pyrimidinyl]acetic acid n/a C18H17FN4O3S 详情 详情
Extended Information