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Sodium hydride → 1-(2-Methoxyethoxy)methyl-2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine

HRID 34400
ノート
印刷プレビュー

反応式

HRID 34400 の反応式
[CH3:1][C:2]1[NH:3][C:4]([CH3:25])=[C:5]([C:21]([O:23][CH3:24])=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9].[CH3:26][O:27][CH2:28][CH2:29][O:30][CH2:31]Cl.[H-].[Na+]>CN(C=O)C>[CH3:26][O:27][CH2:28][CH2:29][O:30][CH2:31][N:3]1[C:4]([CH3:25])=[C:5]([C:21]([O:23][CH3:24])=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:2]1[CH3:1]
参加物反応条件実験手順出典と根拠反応ノート

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 775901-(Chloromethoxy)-2-methoxyethaneHCID 89082m-Nifedipine

生成物 1

HCID 142087931-(2-Methoxyethoxy)methyl-2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

The presently preferred method for preparing compounds of the invention is set forth in Scheme VI. An intermediate dihydropyridine diester derivative of formula 16 is prepared by means known in the art, e.g., by following the Hantzch method (Ann. Chim., 215, 1 (1882)), using reactants selected to provide the desired R1, R2, R3, X1, and X2 substitutions. The diester is then N-protected by mixing with a slight molar excess (preferably between 1.1 and 1.3 moles per mole of compound of formula 16) α-alkoxy-ω-chloromethoxyalkane and a slight molar excess (about 1.2 mol/mol 16) of a suitable strong base, preferably NaH, in a polar, aprotic solvent (preferably DMF or DMSO) at -10° to 0° C. for between about 60 and about 100 minutes, followed by warming to about room temperature for between about 50 and 200 minutes (preferably about 60 minutes), to produce an N-protected diester of formula 17. For example, 1 mol 2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine is reacted with 1.2 mol 1-methoxy-2-chloromethoxyethane and 1.2 mol NaH in DMF at -10° C. for 1 hour, then allowed to warm to about 25° C. for 1 hour to produce 1-(2-methoxyethoxy)methyl-2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine (17). (Scheme VI, Step 1)

出典と根拠

ORDレコード
ord-626483c809014b6689ea6eae9874e9ff
出典データセット
uspto-grants-1988_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US04761420

反応ノート

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