N-Methylglycine; Sarcosine; 2-(Methylamino)acetic acid -Drug Synthesis Database

【结构式】

【分子编号】10429

【品名】N-Methylglycine; Sarcosine; 2-(Methylamino)acetic acid

【CA登记号】107-97-1

【分子式】C₃H₇NO₂

【分子量】89.09412

【元素组成】C 40.44% H 7.92% N 15.72% O 35.92%

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：(V)

The oxidation of 2-nitro-5-fluorotoluene (I) with KMnO4 in water gives 2-nitro-5-fluorobenzoic acid (II), which by reduction with H2 over Pd/C in methanol - aqueous HCl yields 2-amino-5-fluorobenzoic acid (III). The reaction of (III) with phosgene in THF aqueous HCl affords 5-fluoroisatoic acid anhydride (IV), which by cyclization with N-methylglycine (V) in OMS at 100 C affords 7-fluoro-4-methyl-3,4-dihydro-2H-1,4-benzodiazepin-2,5(1H)-dione (VI). Finally, this compound is cyclized again with ethyl isocyanacetate (VII) by means of potassium tert-butylate and diethyl chlorophosphate in DMF.

参考文献中间体

合成目标

【1】 Haefely, W.; Hunkeler, W.; Kyburz, E.; Mohler, H.; Pieri, L.; Polc, P.; Gerecke, M. (F. Hoffmann-La Roche AG); Imidazodiazepine derivatives. EP 0027214; GB 2060632; JP 1156968; US 4316839; US 4346033 .
【2】 Blancafort, P.; Castaner, J.; Hillier, K.; Serradell, M.N.; RO-15-1788. Drugs Fut 1982, 7, 6, 402.

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)	20612	4-Fluoro-2-methyl-1-nitrobenzene; 2-Nitro-5-fluorotoluene	446-33-3	C₇H₆FNO₂	详情	详情
(II)	31962	2-Nitro-5-fluorobenzoic acid; 5-Fluoro-2-nitrobenzoic acid	320-98-9	C₇H₄FNO₄	详情	详情
(III)	31963	2-Amino-5-fluorobenzoic acid	446-08-2	C₇H₆FNO₂	详情	详情
(IV)	31964	6-Fluoro-2H-3,1-benzoxazine-2,4(1H)-dione; 5-Fluoroisatoic acid anhydride		C₈H₄FNO₃	详情	详情
(V)	10429	N-Methylglycine; Sarcosine; 2-(Methylamino)acetic acid	107-97-1	C₃H₇NO₂	详情	详情
(VI)	31965	7-Fluoro-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione; 7-Fluoro-4-methyl-3,4-dihydro-2H-1,4-benzodiazepin-2,5(1H)-dione		C₁₀H₉FN₂O₂	详情	详情
(VII)	11877	Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate	105-56-6	C₅H₇NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

7) [12b-14C]-Org-5222: The condensation of labeled sarcosine methyl ester (XVI) (prepared from sarcosine (XV) with SOCl2 and methanol) with 2-(5-chloro-2-phenoxyphenyl)acetyl chloride (XVIII) (prepared from the corresponding acid (XVII) and SOCl2) yields the acylated sarcosine (XIX), which is cyclized by means of potassium tert-butoxide in toluene to the pyrrolidinedione (XX). A further cyclization of (XX) with polyphosphoric acid affords [3a-14C]-11-chloro-2-methyl-2,3-dihydro-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrol-1-one (XXI), which is reduced with Mg in methanol to the trans-isomeric amide (XXII) (along with the cis-isomer, which is separated by HPLC). Finally, the amide (XXII) is reduced with LiAlH4/AlCl3 in ethyl ether.

参考文献中间体

合成目标

【1】 Wagenaars, G.; Vader, J.; Sperling, E.; Terpstra, A.; Kaspersen, F.; Hilberink, P.; Schlachter, I.; The syntheses of radiolabelled Org 5222 and its main metabolite Org 30526. J Label Compd Radiopharm 1994, 34, 9, 845.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXIIa)	10436	(3aS,12bS)-11-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrol-1-one		C₁₇H₁₄ClNO₂	详情	详情
(XXIIb)	44653	(3aS,12bR)-11-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrol-1-one		C₁₇H₁₄ClNO₂	详情	详情
(XXIIa)	44659	(3aS,12bS)-11-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrol-1-one		C₁₇H₁₄ClNO₂	详情	详情
(XXIIb)	44660	(3aS,12bR)-11-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrol-1-one		C₁₇H₁₄ClNO₂	详情	详情
(XV)	10429	N-Methylglycine; Sarcosine; 2-(Methylamino)acetic acid	107-97-1	C₃H₇NO₂	详情	详情
(XV)	44654	2-(methylamino)acetic acid		C₃H₇NO₂	详情	详情
(XVI)	10430	methyl 2-(methylamino)acetate; methyl N-methylglycinate	5473-12-1	C₄H₉NO₂	详情	详情
(XVI)	44655	methyl 2-(methylamino)acetate		C₄H₉NO₂	详情	详情
(XVII)	10431	2-(5-Chloro-2-phenoxyphenyl)acetic acid		C₁₄H₁₁ClO₃	详情	详情
(XVIII)	10432	2-(5-Chloro-2-phenoxyphenyl)acetyl chloride		C₁₄H₁₀Cl₂O₂	详情	详情
(XIX)	10433	methyl 2-[[2-(5-chloro-2-phenoxyphenyl)acetyl](methyl)amino]acetate		C₁₈H₁₈ClNO₄	详情	详情
(XIX)	44656	methyl 2-[[2-(5-chloro-2-phenoxyphenyl)acetyl](methyl)amino]acetate		C₁₈H₁₈ClNO₄	详情	详情
(XX)	10434	3-(5-Chloro-2-phenoxyphenyl)-1-methyl-2,4-pyrrolidinedione		C₁₇H₁₄ClNO₃	详情	详情
(XX)	44657	3-(5-chloro-2-phenoxyphenyl)-1-methyl-2,4-pyrrolidinedione		C₁₇H₁₄ClNO₃	详情	详情
(XXI)	10435	11-Chloro-2-methyl-2,3-dihydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrol-1-one		C₁₇H₁₂ClNO₂	详情	详情
(XXI)	44658	11-chloro-2-methyl-2,3-dihydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrol-1-one		C₁₇H₁₂ClNO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

The reaction of 2-benzoylbenzoic acid (I) with refluxing SOCl2 gives the corresponding acyl chloride (II), which is condensed with 2-(methylamino)acetic acid (III) in benzene to yield the N-(2-benzoylbenzoyl)-N-methylglycine (IV). The reduction of (IV) by means of LiAlH4 in refluxing THF affords the diol (V), which is finally cyclized by means of PPA at 80 C to provide the target benzoxazocine.

参考文献中间体

合成目标

【1】 Galiano Ramos, J.A.; Verde Casanova, M.J.; Fernandez Torija, C. (Instituto de Investigacion y Desarrollo Quimico Biologico SA); Process for the preparation of 1-methyl-5-phenyl-aza-4-oxo-6,7-benzocyclooctane. ES 8104800 .

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)	59365	2-benzophenone carboxylic acid; 2-Benzoylbenzoic acid; 2-Carboxybenzophenone; Benzophenone-2-carboxylic acid; O-benzoylbenzoic acid	85-52-9	C₁₄H₁₀O₃	详情	详情
(II)	59366	2-benzoylbenzoyl chloride		C₁₄H₉ClO₂	详情	详情
(III)	10429	N-Methylglycine; Sarcosine; 2-(Methylamino)acetic acid	107-97-1	C₃H₇NO₂	详情	详情
(IV)	59376	2-[(2-benzoylbenzoyl)(methyl)amino]acetic acid		C₁₇H₁₅NO₄	详情	详情
(V)	59375	2-[{2-[hydroxy(phenyl)methyl]benzyl}(methyl)amino]-1-ethanol		C₁₇H₂₁NO₂	详情	详情

Extended Information