Water → tert-butyl N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidin-2-yl]phenyl]carbamate

HRID 2353623Notes

Reaction equation

HRID 2353623 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][C:22]([O:25][C:26]([NH:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)=[O:27])([CH3:24])[CH3:23].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.COCCOC.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:32]2[CH:31]=[CH:30][C:29]([NH:28][C:26](=[O:27])[O:25][C:22]([CH3:23])([CH3:21])[CH3:24])=[CH:34][CH:33]=2)[N:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 3613184(4-Boc-Aminophenyl)Boronic AcidHCID 575473562-Chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine

Product 1

HCID 59508397tert-butyl N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidin-2-yl]phenyl]carbamateYield 35%

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 (1.0 g, 3.27 mmol) was dissolved in a solution of 18% DMF in a mixture of 7:3:2 DME:water:ethanol (7 mL). [4-[(2-Methylpropan-2-yl)oxycarbonylamino]phenyl]boronic acid (1.165 g, 4.91 mmol), 2M sodium carbonate solution (4 mL) and dichlorobis(triphenylphosphine) palladium catalyst (115 mg, 0.16 mmol) were then added to the solution and refluxed at 90° C. for 5 hours under nitrogen atmosphere. The reaction was allowed to cool to room temp then partitioned between ethyl acetate and water. The organics were dried over magnesium sulphate, filtered and concentrated to dryness. The crude oil was dissolved in dichloromethane and filtered to remove insoluble material. A beige solid precipitated from the filtrates and the filtrates were filtered again. The solid was analysed and found to be the excess boronic acid and the filtrates contained the product and some impurities. The filtrates were purified by chromatography on silica, eluting with 0-40% ethyl acetate in isohexane, to give the desired compound as an orange oil (530 mg).

Workup

  1. temperatureto cool to room temp
  2. customthen partitioned between ethyl acetate and water
  3. dry with materialThe organics were dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. dissolutionThe crude oil was dissolved in dichloromethane
  7. filtrationfiltered
  8. customto remove insoluble material
  9. customA beige solid precipitated from the filtrates
  10. filtrationthe filtrates were filtered again
  11. customThe filtrates were purified by chromatography on silica
  12. washeluting with 0-40% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-66640186472a4e5db6a31912de2458f7
Source dataset
uspto-grants-2010_07
Patent number
US07750003B2

Reaction notes

Loading…