Lithium Hydroxide → HCID 178463387, 화합물

HRID 1620226노트

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HRID 1620226 반응식
[ClH:1].[Cl:2][CH2:3][C:4]1[C:5]([NH:16][CH2:17][CH3:18])=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([O:14][CH3:15])=[CH:9][CH:8]=2.[CH:19]([C:22]1[C:31]2[C:26](=[CH:27][C:28]([O:34][CH3:35])=[C:29]([O:32][CH3:33])[CH:30]=2)[CH:25]=[C:24]([OH:36])[N:23]=1)([CH3:21])[CH3:20].[Li+].[OH-]>C1COCC1.C(Cl)Cl>[ClH:2].[ClH:1].[CH2:17]([NH:16][C:5]1[C:4]([CH2:3][C:25]2[C:26]3[C:31](=[CH:30][C:29]([O:32][CH3:33])=[C:28]([O:34][CH3:35])[CH:27]=3)[C:22]([CH:19]([CH3:20])[CH3:21])=[N:23][C:24]=2[OH:36])=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:14][CH3:15])[CH:11]=2)[N:6]=1)[CH3:18]

참가 물질

6

반응물 3

HCID 3939Lithium HydroxideHCID 681824593-(chloromethyl)-N-ethyl-6-methoxyquinolin-2-amine hydrochlorideHCID 178486705HCID 178486705, 화합물2회

생성물 1

HCID 178463387HCID 178463387, 화합물수율 5%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

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온도
150 °C

실험 절차

To a stirred solution of 3-(chloromethyl)-N-ethyl-6-methoxyquinolin-2-amine hydrochloride (250 mg, 0.87 mmol) in THF (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 1-isopropyl-6,7-dimethoxyisoquinolin-3-ol SIL 32164 (215 mg, 0.87 mmol) followed by a 2 N aq. LiOH solution (0.87 mL, 1.74 mmol) and the mixture was stirred at 150° C. for 1.5 h under microwave irradiation. After cooling to RT, the mixture was diluted with CH2Cl2:MeOH=9:1 (150 mL), washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 0:100) followed by a second purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5) provided, after evaporation and drying, 38 mg of 4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-1-isopropyl-6,7-dimethoxyisoquinolin-3-ol as a brown solid. This free base was dissolved in CH2Cl2 (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.49 M HCl solution in MeOH (0.70 mL). The reaction mixture was stirred for 5 min at RT then concentrated at 40° C. under vacuum to afford 4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-1-isopropyl-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 47 as a yellow solid (24 mg, 5% yield).

후처리

  1. temperatureAfter cooling to RT
  2. washMeOH=9:1 (150 mL), washed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated at 40° C. under vacuum
  6. customPurification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 0:100)
  7. customfollowed by a second purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5)
  8. customprovided
  9. customafter evaporation
  10. customdrying
  11. dissolutionThis free base was dissolved in CH2Cl2 (2 mL) in a 10 mL round-bottomed flask
  12. customequipped with a magnetic stirrer before addition of a 0.49 M HCl solution in MeOH (0.70 mL)
  13. stirringThe reaction mixture was stirred for 5 min at RT
  14. concentrationthen concentrated at 40° C. under vacuum

출처 및 근거

ORD 기록
ord-a8f4bf2fb9f74de38b5eaab5c965b280
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772316B2

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