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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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Sodium hydride → 6-(5-Chloro-1,8-naphthyridin-2-yl)-2,3,6,7-tetrahydro-7-oxo-5H-1,4-dithiino(2,3-c)pyrrol-5-yl 4-methylpiperazine-1-carboxylate

HRID 1604965
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HRID 1604965 반응식
[Cl:1][C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([N:12]1[CH:16]([OH:17])[C:15]3[S:18][CH2:19][CH2:20][S:21][C:14]=3[C:13]1=[O:22])=[N:7]2.[H-].[Na+].Cl[C:26]([N:28]1[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]1)=[O:27]>CN(C)C=O.CS(O)(=O)=O.C(#N)C.C(Cl)Cl>[Cl:1][C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([N:12]1[CH:13]([O:22][C:26]([N:28]3[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]3)=[O:27])[C:14]3[S:21][CH2:20][CH2:19][S:18][C:15]=3[C:16]1=[O:17])=[N:7]2
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참가 물질

8

반응물 3

HCID 24758Sodium hydrideHCID 30169354-Methyl-1-piperazinecarbonyl chlorideHCID 21527040HCID 21527040, 화합물

생성물 1

HCID 1038386-(5-Chloro-1,8-naphthyridin-2-yl)-2,3,6,7-tetrahydro-7-oxo-5H-1,4-dithiino(2,3-c)pyrrol-5-yl 4-methylpiperazine-1-carboxylate수율 49.5%

시약·촉매·용매 4

HCID 6228Dimethylformamide용매
2회
HCID 6342Acetonitrile용매
HCID 6344Dichloromethane용매
HCID 6395Methanesulfonic Acid용매

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온도
5 °C

실험 절차

6-(5-Chloro-1,8-naphthyridin-2-yl)-5-hydroxy-7-oxo-2,3,6,7-tetrahydro-1,4-dithiino[2,3-c]pyrrole (11.9 g.) is added, at 0° C., to a suspension of sodium hydride (1.2 g.) in anhydrous dimethylformamide (120 cc.). The reaction mixture is stirred for 1 hour at 5° C., and 1-chlorocarbonyl-4-methylpiperazine (16.6 g.) dissolved in anhydrous dimethylformamide (80 cc.) is then added. After stirring for 21/2 hours at 5° C., the crystals which have appeared are filtered off and washed twice with diethyl ether (60 cc.). The product thus isolated is dissolved in an ice-cold 2N aqueous solution of methanesulphonic acid (200 cc.). The aqueous acid solution is washed with diethyl ether (80 cc.), and rendered alkaline by adding an excess of 10N sodium hydroxide solution. The oil which separates out is extracted twice with methylene chloride (total 400 cc.). The organic solution is washed three times with distilled water (total 240 cc.), dried over anhydrous sodium sulphate, treated with decolourising charcoal (0.2 g.) and evaporated. The crystals obtained (10.1 g.), m.p. 238° C., are dissolved in a boiling mixture of acetonitrile (200 cc.) and methylene chloride (180 cc.). After distilling off the methylene chloride and then cooling the residue for 1 hour at 2° C., the crystals which have appeared are filtered off, washed twice with ice-cold acetonitrile (total 40 cc.) and dried under reduced pressure (20 mm. Hg). 6-(5-Chloro-1,8-naphthyridin-2-yl)-5-(4-methylpiperazin-1-yl)carbonyloxy-7-oxo-2,3,6,7-tetrahydro-1,4-dithiino[2,3-c]pyrrole (8.0 g.), melting at 240° C., is thus obtained.

후처리

  1. additionis then added
  2. stirringAfter stirring for 21/2 hours at 5° C.
  3. filtrationthe crystals which have appeared are filtered off
  4. washwashed twice with diethyl ether (60 cc.)
  5. customThe product thus isolated
  6. washThe aqueous acid solution is washed with diethyl ether (80 cc.)
  7. additionby adding an excess of 10N sodium hydroxide solution
  8. extractionThe oil which separates out is extracted twice with methylene chloride (total 400 cc.)
  9. washThe organic solution is washed three times with distilled water (total 240 cc.)
  10. dry with materialdried over anhydrous sodium sulphate
  11. additiontreated with decolourising charcoal (0.2 g.)
  12. customevaporated
  13. customThe crystals obtained (10.1 g.), m.p. 238° C.
  14. distillationAfter distilling off the methylene chloride
  15. temperaturecooling the residue for 1 hour at 2° C.
  16. filtrationthe crystals which have appeared are filtered off
  17. washwashed twice with ice-cold acetonitrile (total 40 cc.)
  18. customdried under reduced pressure (20 mm. Hg)

출처 및 근거

ORD 기록
ord-3d3f1f0db5d3498789c17b03eafd4e6a
출처 데이터셋
uspto-grants-1976_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US03948917

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