Methanesulfonic Acid → Trifluoroacetic acid

HRID 1398472Notes

Reaction equation

HRID 1398472 reaction equation
[Cl:1][C:2]1[C:26]([O:27][CH2:28][C@@H:29]([NH:34]C(=O)OC(C)(C)C)[CH2:30][CH:31]([CH3:33])[CH3:32])=[C:25]([F:42])[C:5]2[N:6](CC3C=CC(OC)=CC=3)[C:7](=[O:15])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][C:9]=3[CH3:14].CS(O)(=O)=O.[C:48]([OH:54])([C:50]([F:53])([F:52])[F:51])=[O:49]>>[NH2:34][C@@H:29]([CH2:30][CH:31]([CH3:33])[CH3:32])[CH2:28][O:27][C:26]1[C:2]([Cl:1])=[CH:3][C:4]2[C:13]3[C:8](=[C:9]([CH3:14])[N:10]=[CH:11][CH:12]=3)[C:7](=[O:15])[NH:6][C:5]=2[C:25]=1[F:42].[C:48]([OH:54])([C:50]([F:53])([F:52])[F:51])=[O:49]

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 6422Trifluoroacetic acidHCID 86710443HCID 86710443, compound

Product 2

HCID 6422Trifluoroacetic acidYield 34.4%HCID 73214595(S)-8-((2-amino-4-methylpentyl)oxy)-9-chloro-7-fluoro-4-methylbenzo[c][2,7]naphthyridin-5(6H)-one

Conditions

Temperature
70 °C

Procedure

To a solution of (S)-tert-butyl (1-((9-chloro-7-fluoro-6-(4-methoxybenzyl)-4-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.08 g, 0.037 mmol) in TFA (8 mL) cooled to 0° C. was added methanesulfonic acid (0.243 μl, 3.75 μmol). The reaction mixture was then heated at 70° C. for 2 h. The volatiles were evaporated. The residue was taken up in water and neutralized with 10% aqueous NaHCO3. The solution was extracted with EtOAc (3×15 mL). The combined organic layers were washed with brine (1×15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Column: X-Bridge (19×150 mm) 5 μm, Flow rate: 15 ml/min; Solvent A: 0.01% TFA, Solvent B: ACN) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-9-chloro-7-fluoro-4-methylbenzo[c][2,7]naphthyridin-5(6H)-one, 3 TFA (9.5 mg, 0.013 mmol, 34.4% yield) as an off-white solid. LC/MS (ESI) m/e 378.0 [(M+H)+, calcd for C19H22ClFN3O2 378.1]; LC/MS retention time (method C): tR=2.02 min; HPLC retention time (method A): tR=7.47 min; HPLC retention time (method B): tR=8.41 min; 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.70 (d, J=6.0 Hz, 1H), 8.40 (d, J=2.0 Hz, 1H), 8.35 (d, J=6.3 Hz, 1H), 4.49 (dd, J=10.7, 2.6 Hz, 1H), 4.35 (dd, J=10.5, 5.8 Hz, 1H), 3.75-3.69 (m, 1H), 3.14 (s, 3H), 1.90-1.74 (m, 2H), 1.70-1.56 (m, 1H), 1.04 (d, J=2.3 Hz, 3H), 1.03 (d, J=2.5 Hz, 3H).

Workup

  1. customThe volatiles were evaporated
  2. extractionThe solution was extracted with EtOAc (3×15 mL)
  3. washThe combined organic layers were washed with brine (1×15 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC (Column: X-Bridge (19×150 mm) 5 μm, Flow rate: 15 ml/min; Solvent A: 0.01% TFA, Solvent B: ACN)

Sources & evidence

ORD record
ord-9ca617b1c81644eea97fa37ae23a406e
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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