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Dichloromethane → 6-(7-Chloro-1,8-naphthyridin-2-yl)-6,7-dihydro-7-oxo-5H-pyrrole(3,4-b)pyrazin-5-yl dimethylcarbamate

HRID 66339
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HRID 66339 반응식
[CH3:1][N:2]([CH3:6])[C:3](Cl)=[O:4].C(N(CC)CC)C.[Cl:14][C:15]1[N:24]=[C:23]2[C:18]([CH:19]=[CH:20][C:21]([N:25]3[CH:33]([OH:34])[C:32]4[C:27](=[N:28][CH:29]=[CH:30][N:31]=4)[C:26]3=[O:35])=[N:22]2)=[CH:17][CH:16]=1.C(Cl)Cl>C(#N)C.CN(C)C=O.O.N1C=CC=CC=1>[Cl:14][C:15]1[N:24]=[C:23]2[C:18]([CH:19]=[CH:20][C:21]([N:25]3[CH:33]([O:34][C:3]([N:2]([CH3:6])[CH3:1])=[O:4])[C:32]4[C:27](=[N:28][CH:29]=[CH:30][N:31]=4)[C:26]3=[O:35])=[N:22]2)=[CH:17][CH:16]=1
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참가 물질

9

반응물 4

HCID 6344DichloromethaneHCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 64531286-(7-chloro-1,8-naphthyridin-2-yl)-6,7-dihydro-7-hydroxy-5H-pyrrolo[3,4-b]pyrazin-5-one

생성물 1

HCID 227547576-(7-Chloro-1,8-naphthyridin-2-yl)-6,7-dihydro-7-oxo-5H-pyrrole(3,4-b)pyrazin-5-yl dimethylcarbamate수율 62.4%

시약·촉매·용매 4

HCID 962Water용매2회HCID 1049Pyridine용매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매

실험 절차

Dimethylcarbamoyl chloride (4.85 g.) and triethylamine (4.55 g.) are added successively to a suspension of 6-(7-chloro-1,8-naphthyridin-2-yl)-5-hydroxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (4.7 g.) in a mixture of anhydrous methylene chloride (47 cc.) and anhydrous pyridine (16 cc.). The reaction mixture is heated at the reflux temperature for 2 hours, and is then cooled and poured into water (180 cc.). A slight amount of insoluble matter is filtered off and the aqueous layer is decanted off and washed with methylene chloride (2 × 50 cc.) by successive decantations. The combined organic layers are washed by successive decantations with 1N sodium hydroxide solution (2 × 30 cc.) and water (2 × 33 cc.), dried with anhydrous sodium sulphate in the presence of decolourising charcoal, filtered and evaporated to dryness under reduced pressure. The residue obtained is taken up in acetonitrile (20 cc.) and the insoluble product is filtered off and washed with acetonitrile (3 × 2 cc.). Recrystallisation of this product from dimethylformamide (14 cc.) gives a solvated product (4.1 g.). This product is dissolved in dimethylformamide (100 cc.) at a temperature of about 70° C. The solution thus obtained is poured into water (1,200 cc.) and the insoluble product is filtered off and washed with water (5 × 20 cc.). After drying, 6-(7-chloro-1,8-naphthyridin-2-yl)-5-dimethylaminocarbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (3.6 g.), melting at 270° C., is obtained.

후처리

  1. temperatureThe reaction mixture is heated at the reflux temperature for 2 hours
  2. temperatureis then cooled
  3. filtrationA slight amount of insoluble matter is filtered off
  4. customthe aqueous layer is decanted off
  5. washwashed with methylene chloride (2 × 50 cc.) by successive decantations
  6. washThe combined organic layers are washed by successive decantations with 1N sodium hydroxide solution (2 × 30 cc.) and water (2 × 33 cc.)
  7. dry with materialdried with anhydrous sodium sulphate in the presence of decolourising charcoal
  8. filtrationfiltered
  9. customevaporated to dryness under reduced pressure
  10. customThe residue obtained
  11. filtrationthe insoluble product is filtered off
  12. washwashed with acetonitrile (3 × 2 cc.)
  13. customRecrystallisation of this product from dimethylformamide (14 cc.)
  14. customgives a solvated product (4.1 g.)
  15. customThe solution thus obtained
  16. filtrationthe insoluble product is filtered off
  17. washwashed with water (5 × 20 cc.)
  18. customAfter drying

출처 및 근거

ORD 기록
ord-9a3b6c1266164486843ea24d1d38d68f
출처 데이터셋
uspto-grants-1978_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US04131674

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