Oxalyl chloride → 3-(1-methyl-1H-indol-3-yl)-4-(1-methyl-6-morpholin-4-yl-1H-indol-3-yl)pyrrole 2,5-dione

HRID 651759

반응식

HRID 651759 반응식
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[CH:9]=2)[CH:4]=[CH:3]1.[C:17](Cl)(=[O:21])[C:18](Cl)=O.Cl.C([O:27][C:28](=[NH:40])[CH2:29][C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[N:32]([CH3:39])[CH:31]=1)(C)C.CC1C=CC(S(O)(=O)=O)=CC=1.O>C(Cl)Cl.CCOC(C)=O.CCN(CC)CC>[CH3:39][N:32]1[C:33]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:30]([C:29]2[C:28](=[O:27])[NH:40][C:17](=[O:21])[C:18]=2[C:4]2[C:5]3[C:10](=[CH:9][C:8]([N:11]4[CH2:12][CH2:13][O:14][CH2:15][CH2:16]4)=[CH:7][CH:6]=3)[N:2]([CH3:1])[CH:3]=2)=[CH:31]1

참가 물질

8

반응물 4

HCID 65578Oxalyl chlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 217090601-methyl-6-morpholin-4-yl-1H-indoleHCID 22907276Isopropyl 1-methyl-3-indoleacetimidate hydrochloride

생성물 1

HCID 101141633-(1-methyl-1H-indol-3-yl)-4-(1-methyl-6-morpholin-4-yl-1H-indol-3-yl)pyrrole 2,5-dione수율 31%

시약·촉매·용매 3

HCID 6344Dichloromethane용매2회HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

A solution of 1-methyl-6-morpholin-4-yl-1H-indole (0.50 g, 2.31 mmol) in CH2Cl2 (5 mL) (dried over 3A° molecular sieves) was cooled to 0° C. Oxalyl chloride (0.4 mL, 4.62 mmol), was added dropwise over 5 min. The mixture was stirred at 0° C. for 4 h and evaporated. The residual solid was triturated with ether, filtered, washed with ether and dried under vacuum for 30 min. 1-Methyl -3-indoleacetimidic acid isopropyl ester hydrochloride (0.58 g, 2.20 mmol) and CH2Cl2 (9 mL) were added to the yellow solid at 0° C. Et3N (dried over 3A° molecular sieve) (1.8 mL) was added dropwise over 10 min. and then the orange-red mixture was stirred at room temperature overnight. The mixture was diluted with EtOAc, washed with 1 N NaOH and the aqueous layer was back-extracted with EtOAc. The combined organic extracts were washed with brine, dried (K2CO3) and evaporated. The residue was dissolved in MeOH (100 mL) containing TsOH.H2O (3.30 g, 17.3 mmol ) and the mixture was stirred at room temperature for 4 h. After the solvents were removed under reduced pressure the residue was diluted with EtOAc (500 mL) and made basic using aqueous NaHCO3. The organic layer was separated and the aqueous layer was back extracted with EtOAc. The combined organic extracts were washed with brine, dried (MgSO4), and evaporated. Chromatography of the residue over silica gel using 30-70% EtOAc/hexanes gave 3-(1-methyl-1H-indol-3-yl)-4-(1-methyl-6-morpholin-4-yl-1H-indol-3-yl)pyrrole 2,5-dione (0.30 g, 30%) as an orange solid.

후처리

  1. customevaporated
  2. customThe residual solid was triturated with ether
  3. filtrationfiltered
  4. washwashed with ether
  5. customdried under vacuum for 30 min
  6. stirringthe orange-red mixture was stirred at room temperature overnight
  7. washwashed with 1 N NaOH
  8. extractionthe aqueous layer was back-extracted with EtOAc
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried (K2CO3)
  11. customevaporated
  12. dissolutionThe residue was dissolved in MeOH (100 mL)
  13. stirringthe mixture was stirred at room temperature for 4 h
  14. customAfter the solvents were removed under reduced pressure the residue
  15. additionwas diluted with EtOAc (500 mL)
  16. customThe organic layer was separated
  17. extractionthe aqueous layer was back extracted with EtOAc
  18. washThe combined organic extracts were washed with brine
  19. dry with materialdried (MgSO4)
  20. customevaporated

출처 및 근거

ORD 기록
ord-89c7d334720140daa5b1dafc9fed2444
출처 데이터셋
uspto-grants-2001_08
특허 번호
US06281356B1

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