(4-fluorophenyl)[(4-methylphenyl)sulfonyl]methylformamide -Drug Synthesis Database

【结构式】

【分子编号】25594

【品名】(4-fluorophenyl)[(4-methylphenyl)sulfonyl]methylformamide

【CA登记号】

【分子式】C₁₅H₁₄FNO₃S

【分子量】307.3455032

【元素组成】C 58.62% H 4.59% F 6.18% N 4.56% O 15.62% S 10.43%

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：(III)

The condensation of p- fluorobenzaldehyde (I) with p-toluenesulfinic acid (II) in the presence of camphorsulfonic acid in formamide produced the tosylmethyl formamide (III). This was dehydrated to the required isocyanide (IV) using POCl3 and Et3N in cold dimethoxyethane.

参考文献中间体

合成目标

【1】 Adams, J.L.; Garigipati, R.S. (SmithKline Beecham plc); Novel cycloalkyl substd. imidazoles. EP 0883402; WO 9725047 .
【2】 Adams, J.L.; Garigipati, R.S.; Sorenson, M.E. (SmithKline Beecham plc); Novel cycloalkyl substd. imidazoles. EP 0889726; JP 2000503304; WO 9725048 .
【3】 Boehm, J.C.; Garigipati, R.S.; Adams, J.L. (SmithKline Beecham Corp.); Novel cycloalkyl substd. imidazoles. EP 1019396; WO 9901452 .

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)	12337	4-fluorobenzaldehyde	459-57-4	C₇H₅FO	详情	详情
(II)	25593	4-methylbenzenesulfinic acid		C₇H₈O₂S	详情	详情
(III)	25594	(4-fluorophenyl)[(4-methylphenyl)sulfonyl]methylformamide		C₁₅H₁₄FNO₃S	详情	详情
(IV)	25595	4-Fluoro-alpha-(4-methylphenylsulfonyl)benzyl isocyanide		C₁₅H₁₂FNO₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

In a related procedure, condensation of 4-fluorobenzaldehyde (IX) with formamide and p-toluenesulfinic acid (XIV) produced the tosyl formamide (XV), which was dehydrated by means of POCl3 and Et3N to give isonitrile (XVI). Imidazole (XIII) was then obtained by reaction of this isonitrile with imine (VIII). Finally, the Boc protecting group of (XIII) was removed by acid treatment as above.

参考文献中间体

合成目标

【1】 Adams, J.L.; Gallagher, T.F.; Garigipati, R.S.; Boehm, J.C.; Sisko, J.; Peng, Z.-Q.; Lee, J.C.-L. (SmithKline Beecham plc); Certain 1,4,5-tri-substd. imidazole cpds. useful as cytokine. EP 0809499; JP 1998512555; US 5593992; WO 9621452 .
【2】 Garigipati, R.S.; Adams, J.L.; Boehm, J.C. (SmithKline Beecham Corp.); Pyridyl imidazole cpds. and compsns.. US 5670527 .
【3】 Adams, J.L.; Boehm, J.C.; Imidazole cpds., use and process of making. US 5593991 .

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)	28415	tert-butyl 4-([(Z)-[2-(methylamino)-4-pyrimidinyl]methylidene]amino)-1-piperidinecarboxylate		C₁₆H₂₅N₅O₂	详情	详情
(IX)	12337	4-fluorobenzaldehyde	459-57-4	C₇H₅FO	详情	详情
(XIII)	28417	tert-butyl 4-[4-(4-fluorophenyl)-5-[2-(methylamino)-4-pyrimidinyl]-1H-imidazol-1-yl]-1-piperidinecarboxylate		C₂₄H₂₉FN₆O₂	详情	详情
(XIV)	25593	4-methylbenzenesulfinic acid		C₇H₈O₂S	详情	详情
(XV)	25594	(4-fluorophenyl)[(4-methylphenyl)sulfonyl]methylformamide		C₁₅H₁₄FNO₃S	详情	详情
(XVI)	25595	4-Fluoro-alpha-(4-methylphenylsulfonyl)benzyl isocyanide		C₁₅H₁₂FNO₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Two related syntheses have been reported for this compound. The intermediate alpha-tosyl-(4-fluorobenzyl)isonitrile (V) was prepared by condensation of 4-fluorobenzaldehyde (I), p-toluenesulfinic acid (II) and formamide (III) in the presence of chlorotrimethylsilane (1-4), followed by dehydration of the resulting formamide derivative (IV) with POCl3 and triethylamine.

参考文献中间体

合成目标

【1】 Sisko, J.; A one-pot synthesis of 1-(2,2,6,6-tetramethyl-4-piperidinyl)-4-(4-fluorophenyl)-5-(2-amino-4-pyrimidinyl)imidazole: A potent inhibitor of P38 MAP kinase. J Org Chem 1998, 63, 13, 4529.
【2】 Adams, J.L.; Gallagher, T.F.; Garigipati, R.S.; Boehm, J.C.; Sisko, J.; Peng, Z.-Q.; Lee, J.C.-L. (SmithKline Beecham plc); Certain 1,4,5-tri-substd. imidazole cpds. useful as cytokine. EP 0809499; JP 1998512555; US 5593992; WO 9621452 .
【3】 Adams, J.L.; Boehm, J.C.; Imidazole cpds., use and process of making. US 5593991 .

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)	12337	4-fluorobenzaldehyde	459-57-4	C₇H₅FO	详情	详情
(II)	25593	4-methylbenzenesulfinic acid		C₇H₈O₂S	详情	详情
(IV)	25594	(4-fluorophenyl)[(4-methylphenyl)sulfonyl]methylformamide		C₁₅H₁₄FNO₃S	详情	详情
(V)	25595	4-Fluoro-alpha-(4-methylphenylsulfonyl)benzyl isocyanide		C₁₅H₁₂FNO₂S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(III)

Condensation between p-fluorobenzaldehyde (I), p-toluenesulfinic acid (II) and formamide in the presence of camphorsulfonic acid afforded 4-fluorophenyltosylmethyl formamide (III). Subsequent dehydration of (III) by means of POCl3 and Et3N produced isonitrile (IV). Imine (VII) was prepared by condensation of pyridine-4-carboxaldehyde (V) with 1-Boc-4-aminopiperidine (VI) using MgSO4 as the dehydrating reagent. Dipolar cycloaddition of this imine with the anion of tosyl isonitrile (IV) generated the trisubstituted imidazole (VIII). Finally, acid cleavage of the Boc protecting group furnished the title compound.

参考文献中间体

合成目标

【1】 Adams, J.L.; Gallagher, T.F.; Garigipati, R.S.; Boehm, J.C.; Sisko, J.; Peng, Z.-Q.; Lee, J.C.-L. (SmithKline Beecham plc); Certain 1,4,5-tri-substd. imidazole cpds. useful as cytokine. EP 0809499; JP 1998512555; US 5593992; WO 9621452 .
【2】 Garigipati, R.S.; Adams, J.L.; Boehm, J.C. (SmithKline Beecham Corp.); Pyridyl imidazole cpds. and compsns.. US 5670527 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	16598	Formamide	75-12-7	CH₃NO	详情	详情
(I)	12337	4-fluorobenzaldehyde	459-57-4	C₇H₅FO	详情	详情
(II)	25593	4-methylbenzenesulfinic acid		C₇H₈O₂S	详情	详情
(III)	25594	(4-fluorophenyl)[(4-methylphenyl)sulfonyl]methylformamide		C₁₅H₁₄FNO₃S	详情	详情
(IV)	25595	4-Fluoro-alpha-(4-methylphenylsulfonyl)benzyl isocyanide		C₁₅H₁₂FNO₂S	详情	详情
(V)	17203	4-Pyridinecarboxaldehyde; isonicotinaldehyde	872-85-5	C₆H₅NO	详情	详情
(VI)	28414	4-Amino-1-N-Boc-piperidine; tert-butyl 4-amino-1-piperidinecarboxylate; N-Boc-4-aminopiperidine	87120-72-7	C₁₀H₂₀N₂O₂	详情	详情
(VII)	34886	tert-butyl 4-[[(Z)-4-pyridinylmethylidene]amino]-1-piperidinecarboxylate		C₁₆H₂₃N₃O₂	详情	详情
(VIII)	34887	tert-butyl 4-[4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazol-1-yl]-1-piperidinecarboxylate		C₂₄H₂₇FN₄O₂	详情	详情

Extended Information