Water → N-(4-(4-fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

HRID 2207005Notes

Reaction equation

HRID 2207005 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH3:14])=[C:12]([CH:15]([CH3:17])[CH3:16])[N:11]=[C:10]([N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])[N:9]=2)=[CH:4][CH:3]=1.BrN1C(=[O:30])CCC1=O.C([O-])(O)=O.[Na+].O>C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:13]([CH2:14][OH:30])=[C:12]([CH:15]([CH3:17])[CH3:16])[N:11]=[C:10]([N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])[N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 20771262N-[4-(4-Fluorophenyl)-5-methyl-6-(1-methylethyl)-2-pyrimidinyl]-N-methylmethanesulfonamide

Product 1

HCID 9819937N-(4-(4-fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamideYield 95%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

N-(4-(4-fluorophenyl)-5-methyl-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide (112.5 mg, 0.33 mmol, 1 equiv.) and N-bromosuccinimide (NBS) (118.7 mg, 0.66 mmol, 2 equiv.) were dissolved in 2 mL of acetonitrile. The mixture was irradiated with light of a wavelength A=310 nm for 4 hours at ambient temperature (about 20° C.). The obtained yellow solution was diluted with 1 mL of acetonitrile. After 2 mL of saturated NaHCO3 solution was added, the obtained mixture was further stirred under reflux for 4 hours. Then the mixture was cooled to room temperature, water (10 mL) was added and the mixture was extracted with CH2Cl2 (3×10 mL). The combined organic phases were washed with 10 mL of brine, and the obtained solution was dried with Na2SO4. Solvent was removed under the reduced pressure to give 110.8 mg (95%) of crude N-(4-(4-fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide (III) which contained 77% of N-(4-(4-fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide (III) as determined by 1H-NMR integral. This product can be further purified by crystallization from MTBE/hexane mixture to afford pure material (HPLC area %=99.6) with Tm=140-141° C.

Workup

  1. customThe mixture was irradiated with light of a wavelength A=310 nm for 4 hours at ambient temperature (about 20° C.)
  2. temperatureunder reflux for 4 hours
  3. extractionthe mixture was extracted with CH2Cl2 (3×10 mL)
  4. washThe combined organic phases were washed with 10 mL of brine
  5. dry with materialthe obtained solution was dried with Na2SO4
  6. customSolvent was removed under the reduced pressure

Sources & evidence

ORD record
ord-4251d261e916478c8bad7eca76b4057d
Source dataset
uspto-grants-2016_06
Patent number
US09376397B2

Reaction notes

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