Methanol → HCID 90333612, compound

HRID 595718Notes

Reaction equation

HRID 595718 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH:7]([CH2:12]SC)[N:6]3[C:15]4[CH:16]=[CH:17][CH:18]=[C:19]([F:22])[C:20]=4[CH:21]=[C:5]3[C:4]=2[N:3]=1.O[O:24][S:25]([O-:27])=O.[K+].[CH3:29]O>O>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH:7]([CH2:12][S:25]([CH3:29])(=[O:27])=[O:24])[N:6]3[C:15]4[CH:16]=[CH:17][CH:18]=[C:19]([F:22])[C:20]=4[CH:21]=[C:5]3[C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 23707502Potassium hydroxy sulfiteHCID 90333613HCID 90333613, compound

Product 1

HCID 90333612HCID 90333612, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
25 °C

Procedure

To a degassed solution of 2-chloro-11-fluoro-6-((methylthio)methyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (100 mg, 0.3 mmol) in MeOH (2 mL) was added a solution of Oxone (185 mg, 0.3 mmol) in H2O (2 mL) at 0° C., and the mixture was stirred at 25° C. for 24 h. Then the mixture was diluted with water (5 mL) and extracted with EtOAc (5 mL×3). The combined organic layer was washed with brine (10 mL), dried over Na2SO4 and concentrated. The residue was purified by column chromatography (DCM:EA=10:1) to afford the desired product of 2-chloro-11-fluoro-6-((methylsulfonyl)methyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (70 mg, yield: 64%). 1H-NMR (CDCl3, 400 MHz) δ 7.62 (d, J=7.6 Hz, 1H), 7.43 (s, 1H), 7.22˜7.29 (m, 3H), 6.83˜6.89 (m, 1H), 5.45˜5.51 (m, 1H), 3.51˜3.62 (m, 2H), 3.14˜3.21 (m, 1H), 2.97˜3.05 (m, 1H), 2.84 (s, 3H). MS (M+H)+: 365/367.

Workup

  1. extractionextracted with EtOAc (5 mL×3)
  2. washThe combined organic layer was washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (DCM:EA=10:1)

Sources & evidence

ORD record
ord-b2a66130b7df4becb2cc175a9f5a3f4b
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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