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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
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HRID 34400 반응식
[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]
참가 물질반응 조건실험 절차출처 및 근거반응 노트

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
25 °C

실험 절차

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)

출처 및 근거

ORD 기록
ord-626483c809014b6689ea6eae9874e9ff
출처 데이터셋
uspto-grants-1988_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US04761420

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