Methanol → HCID 58318937, compound

HRID 1403185Notes

Reaction equation

HRID 1403185 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][NH:5][C:6]1[C:11]([F:12])=[CH:10][N:9]=[C:8](SC)[N:7]=1.O[O:20][S:21]([O-:23])=O.[K+].S(=O)(O)[O-].[Na+].[CH3:30]O>O>[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][NH:5][C:6]1[C:11]([F:12])=[CH:10][N:9]=[C:8]([S:21]([CH3:30])(=[O:23])=[O:20])[N:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 23665763Sodium BisulfiteHCID 23707502Potassium hydroxy sulfiteHCID 58318928HCID 58318928, compound

Product 1

HCID 58318937HCID 58318937, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of (2-fluorobenzyl)-(5-fluoro-2-methylsulfanylpyrimidin-4-yl)amine (2.10 g, 7.86 mmol) in MeOH (26 mL) was added a solution of OXONE™ (10.14 g, 16.5 mmol) in H2O (52 mL) dropwise over a 20 min period at −45° C., and the resulting mixture was slowly warmed to 10° C. over a period of 14 h. The mixture was treated with sodium bisulfite (−3 g) and the majority of the MeOH was removed on the rotary evaporator. The aqueous residue was extracted with EtOAc (3×150 mL), and the organic extracts were combined, washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated to give a peach solid. The solid was purified by flash chromatography (40 g SiO2; 0→100% EtOAc/hexanes) to give 2-fluorobenzyl-(5-fluoro-2-methanesulfonylpyrimidin-4-yl)amine (1.99 g, 85%) as a white solid: mp 105-107° C.; 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J=2.9 Hz, 1H), 7.46 (td, J=7.6, 1.7 Hz, 1H), 7.31 (m, 1H), 7.14 (td, J=7.5, 1.1 Hz, 1H), 7.08 (m, 1H), 5.89 (s, 1H), 4.82 (d, J=6.0 Hz, 2H), 3.25 (s, 3H); CIMS m/z 299 ([M]+).

Workup

  1. customthe majority of the MeOH was removed on the rotary evaporator
  2. extractionThe aqueous residue was extracted with EtOAc (3×150 mL)
  3. washwashed with brine (100 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a peach solid
  8. customThe solid was purified by flash chromatography (40 g SiO2; 0→100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7cb19a881c1547af8d020f2eb5c2013d
Source dataset
uspto-grants-2014_12
Patent number
US08912207B2

Reaction notes

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