Water → N-methyl-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidin-2-yl]aniline

HRID 2353631

Reaction equation

HRID 2353631 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]2[CH3:14])[CH:5]=[C:4]([CH2:15][S:16]([CH3:19])(=[O:18])=[O:17])[N:3]=1.O.[CH3:21][NH:22][C:23]1[CH:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C(COC)OC.C(O)C>[CH3:21][NH:22][C:23]1[CH:28]=[CH:27][C:26]([C:2]2[N:7]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]3[CH3:14])[CH:5]=[C:4]([CH2:15][S:16]([CH3:19])(=[O:18])=[O:17])[N:3]=2)=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 11957892N-methyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 57547356HCID 57547356, compound

Product 1

HCID 59380133N-methyl-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidin-2-yl]anilineYield 90.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

2-Chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine (1.01 g, 3.30 mmol) was dissolved in 18% DMF in 7:3:2 dimethoxy ethane:water:ethanol (7 mL). N-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.00 g, 4.29 mmol), 2M sodium carbonate solution (4 mL) and dichlorobis(triphenylphosphine) palladium (116 mg, 0.16 mmol) were added to the solution. The reaction was refluxed at 90° C. for 3 hours under nitrogen atmosphere then the mixture allowed to cool and partitioned ethyl acetate (30 mL) and water (30 mL). The organic layer was dried over magnesium sulphate, filtered and evaporated to dryness. The brown oil was dissolved in DCM and filtered to remove insoluble material then the filtrate chromatographed on silica, eluting with 0-4% methanol in DCM, to give the desired product as a yellow foam (1.12 g, 90%)

Workup

  1. temperatureto cool
  2. custompartitioned ethyl acetate (30 mL) and water (30 mL)
  3. dry with materialThe organic layer was dried over magnesium sulphate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. dissolutionThe brown oil was dissolved in DCM
  7. filtrationfiltered
  8. customto remove insoluble material
  9. customthe filtrate chromatographed on silica
  10. washeluting with 0-4% methanol in DCM

Sources & evidence

ORD record
ord-19fef6f66f7647aeb4f6d086802b9327
Source dataset
uspto-grants-2010_07
Patent number
US07750003B2

Linked notes

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