Toluene → N-Cyclopropyl-3-fluoro-5-[2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-4-(piperidin-4-ylsulfanyl)-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamide

HRID 906459노트

반응식

HRID 906459 반응식
FC(F)(F)C(O)=O.[Si]([O:15][CH2:16][C:17]([CH3:59])([CH3:58])[CH2:18][N:19]1[CH:28]=[C:27]([S:29][CH:30]2[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]2)[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:43]3[CH:48]=[C:47]([C:49](=[O:54])[NH:50][CH:51]4[CH2:53][CH2:52]4)[CH:46]=[C:45]([F:55])[C:44]=3[CH3:56])[CH:25]=2)[C:20]1=[O:57])(C(C)(C)C)(C)C.C1(C)C=CC=CC=1.C(OCC)C>C(Cl)Cl>[CH:51]1([NH:50][C:49](=[O:54])[C:47]2[CH:48]=[C:43]([C:24]3[CH:25]=[C:26]4[C:21](=[CH:22][CH:23]=3)[C:20](=[O:57])[N:19]([CH2:18][C:17]([CH3:59])([CH3:58])[CH2:16][OH:15])[CH:28]=[C:27]4[S:29][CH:30]3[CH2:31][CH2:32][NH:33][CH2:34][CH2:35]3)[C:44]([CH3:56])=[C:45]([F:55])[CH:46]=2)[CH2:52][CH2:53]1

참가 물질

6

반응물 4

HCID 1140TolueneHCID 3283Diethyl EtherHCID 6422Trifluoroacetic acidHCID 67391538Tert-butyl 4-({2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl}sulfanyl)piperidine-1-carboxylate

생성물 1

HCID 59285264N-Cyclopropyl-3-fluoro-5-[2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-4-(piperidin-4-ylsulfanyl)-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamide수율 39.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Trifluoroacetic Acid (1 mL) was added to a solution of tert-butyl 4-({2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl}sulfanyl)piperidine-1-carboxylate (Example 58d, 0.123 g) in DCM (3 mL). The reaction was stirred at room temperature for 30 min. Toluene (5 mL) was added and the volatiles were removed under reduced pressure. The residue was dissolved in MeOH (1 mL)/DMF (1 mL) and purified by preparative HPLC (Xbridge column using a 95-5% gradient of 0.2% aqueous ammonia in acetonitrile) and after solvent removal, the residue was triturated with diethyl ether. This was dissolved in methanol and purified by preparative HPLC (Sunfire C18 column using a 95-30% gradient of 0.1% aqueous formic acid in methanol run over 16 min). The relevant fractions were lyophilized before the solid was dissolved in methanol and passed through a Stratospheres PL-HCO3 cartridge. The solvent was removed from the resulting filtrate under reduced pressure to give, after trituration with diethyl ether, the title compound (0.035 g).

후처리

  1. customthe volatiles were removed under reduced pressure
  2. dissolutionThe residue was dissolved in MeOH (1 mL)/DMF (1 mL)
  3. custompurified by preparative HPLC (Xbridge column
  4. customafter solvent removal
  5. customthe residue was triturated with diethyl ether
  6. dissolutionThis was dissolved in methanol
  7. custompurified by preparative HPLC (Sunfire C18 column
  8. waitrun over 16 min
  9. dissolutionwas dissolved in methanol
  10. customThe solvent was removed from the resulting filtrate under reduced pressure
  11. customto give

출처 및 근거

ORD 기록
ord-6c3ed9ef1b9a497b892c6985460f023c
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08012980B2

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