Water → (4-{4-[1-Methyl-1-(methylsulfonyl)ethyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-2-yl}phenyl)amine

HRID 2353672Notes

Reaction equation

HRID 2353672 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]([C:15]([CH3:21])([S:17]([CH3:20])(=[O:19])=[O:18])[CH3:16])[N:3]=1.O.CC1(C)C(C)(C)OB([C:31]2[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][CH:32]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C(COC)OC.C(O)C>[CH3:16][C:15]([C:4]1[CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]2[CH3:14])[N:7]=[C:2]([C:31]2[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][CH:32]=2)[N:3]=1)([S:17]([CH3:20])(=[O:19])=[O:18])[CH3:21]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 593802202-chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylpropan-2-yl)pyrimidine

Product 1

HCID 59380004(4-{4-[1-Methyl-1-(methylsulfonyl)ethyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-2-yl}phenyl)amineYield 139.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

(3S)-4-{2-Chloro-6-[1-methyl-1-(methylsulfonyl)ethyl]pyrimidin-4-yl}-3-methylmorpholine (2.2 g, 6.59 mmol) was dissolved in a solution of 18% DMF in a mixture of 7:3:2 dimethoxyethane:water:ethanol (18 mL). [4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (2.17 g, 9.89 mmol), 2M sodium carbonate solution (8 mL) and dichlorobis(triphenylphosphine) palladium catalyst (232 mg, 0.33 mmol) were then added and the reaction refluxed at 90° C. for 2 hours under a nitrogen atmosphere. The reaction was allowed to cool to room temp then partitioned between ethyl acetate (20 mL) and water (20 mL). The organics were dried over magnesium sulphate, filtered and concentrated in vacuo. The crude solid was chromatographed on silica, eluting with 0-10% methanol in DCM to give the desired material as a brown oil (3.6 g).

Workup

  1. temperatureto cool to room temp
  2. customthen partitioned between ethyl acetate (20 mL) and water (20 mL)
  3. dry with materialThe organics were dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude solid was chromatographed on silica
  7. washeluting with 0-10% methanol in DCM

Sources & evidence

ORD record
ord-73244035bc774ccf8521eb3879a9703e
Source dataset
uspto-grants-2010_07
Patent number
US07750003B2

Reaction notes

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