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

HRID 2353630Notes

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.[NH2:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C(COC)OC.C(O)C>[CH3:14][C@H:9]1[CH2:10][O:11][CH2:12][CH2:13][N:8]1[C:6]1[CH:5]=[C:4]([CH2:15][S:16]([CH3:19])(=[O:18])=[O:17])[N:3]=[C:2]([C:26]2[CH:27]=[C:22]([CH:23]=[CH:24][CH:25]=2)[NH2:21])[N:7]=1

Participants

Conditions

Temperature: 90 °C

Procedure

2-Chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine (1.50 g, 4.91 mmol) was dissolved in 18% DMF in 7:3:2 dimethoxyethane:water:ethanol (15 mL). (3-Aminophenyl)boronic acid (1.01 g, 7.36 mmol), 2M sodium carbonate (5 mL) and dichlorobis(triphenylphosphine) palladium (173 mg, 0.25 mmol) were added to the solution. The reaction was refluxed at 90° C. for 18 hours under a nitrogen atmosphere then the reaction allowed to cool and partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was dried over magnesium sulphate, filtered and vacuumed to dryness. The resultant 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 oil (1.61 g).

Workup

temperatureto cool
custompartitioned between ethyl acetate (50 mL) and water (50 mL)
dry with materialThe organic layer was dried over magnesium sulphate
filtrationfiltered
dissolutionThe resultant brown oil was dissolved in DCM
filtrationfiltered
customto remove insoluble material
customthe filtrate chromatographed on silica
washeluting with 0-4% methanol in DCM

Sources & evidence

ORD record: ord-53d981ebf89d49d1a8f8e2d2e3e61c48
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07750003B2

Reaction notes

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