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

HRID 906461Notes

Reaction equation

HRID 906461 reaction equation
FC(F)(F)C(O)=[O:4].[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(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]([CH3:58])([CH3:59])[CH2:16][OH:15])[CH:28]=[C:27]4[S:29]([CH:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)=[O:4])[C:44]([CH3:56])=[C:45]([F:55])[CH:46]=2)[CH2:53][CH2:52]1

Participants

5

Reactant 3

HCID 1140TolueneHCID 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

Product 1

HCID 59285285N-Cyclopropyl-3-fluoro-5-[2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-4-(piperidin-4-ylsulfinyl)-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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 59a, 0.06 g) in DCM (2 mL), and the reaction was stirred at room temperature for 30 min. Toluene (10 mL) was added and the volatiles were removed under reduced pressure (repeated 3×). The residue was purified by preparative HPLC (Phenomenex Gemini column using a 95-5% gradient of 0.1% aqueous NH3 in acetonitrile), and after solvent removal and trituration with diethyl ether gave the title compound (0.01 g).

Workup

  1. customthe volatiles were removed under reduced pressure (repeated 3×)
  2. customThe residue was purified by preparative HPLC (Phenomenex Gemini column
  3. customafter solvent removal and trituration with diethyl ether

Sources & evidence

ORD record
ord-6f63f76573444c03a89861da45498502
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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