Sodium Carbonate → (S)-1-ethyl-3-(4-(6-(5-fluoro-2-(methylsulfonyl)phenyl)-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)urea

HRID 1771544Notes

Reaction equation

HRID 1771544 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([CH3:12])(=[O:11])=[O:10].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Cl[C:37]1[N:42]=[C:41]([N:43]2[CH2:48][CH2:47][O:46][CH2:45][C@@H:44]2[CH3:49])[N:40]=[C:39]([C:50]2[CH:55]=[CH:54][C:53]([NH:56][C:57]([NH:59][CH2:60][CH3:61])=[O:58])=[CH:52][CH:51]=2)[CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.CCO>[CH2:60]([NH:59][C:57]([NH:56][C:53]1[CH:54]=[CH:55][C:50]([C:39]2[CH:38]=[C:37]([C:2]3[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=3[S:9]([CH3:12])(=[O:11])=[O:10])[N:42]=[C:41]([N:43]3[CH2:48][CH2:47][O:46][CH2:45][C@@H:44]3[CH3:49])[N:40]=2)=[CH:51][CH:52]=1)=[O:58])[CH3:61]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 532169842-Bromo-4-fluoro-1-(methylsulfonyl)benzeneHCID 86691150(S)-1-(4-(6-chloro-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)-3-ethylurea2×

Product 1

HCID 53380233(S)-1-ethyl-3-(4-(6-(5-fluoro-2-(methylsulfonyl)phenyl)-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)ureaYield 34%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Procedure

2-bromo-4-fluoro-1-(methylsulfonyl)benzene (117 mg, 0.46 mmol), bis(pinacolato)diboron (123 mg, 0.48 mmol), potassium acetate (135 mg, 1.38 mmol) and bis(diphenylphosphino)-ferrocenedichloropalladium(II)-DCM-complex (19 mg, 0.02 mmol) in dioxane (1.5 mL) were irradiated in a Biotage microwave for 60 min at 120° C. (S)-1-(4-(6-chloro-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)-3-ethylurea (Intermediate 2) (173 mg, 0.46 mmol), sodium carbonate solution (2M aqueous solution, 0.92 mL, 1.84 mmol) and EtOH (0.3 mL) were added and reaction mixture further irradiated in a Biotage microwave for 60 min at 100° C. The reaction mixture was concentrated in vacuo, and the residue suspended in EtOAc (70 mL), washed with water (2×40 mL) followed by brine (40 mL), dried with sodium sulfate and concentrated in vacuo to leave an orange oil. The oil was purified by flash chromatography (0-20% EtOAc in DCM over 60 min) to yield the title compound as an orange solid (80 mg, 34%).

Workup

  1. additionwere added
  2. customreaction mixture
  3. customfurther irradiated in a Biotage microwave for 60 min at 100° C
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. washwashed with water (2×40 mL)
  6. dry with materialdried with sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customto leave an orange oil
  9. customThe oil was purified by flash chromatography (0-20% EtOAc in DCM over 60 min)

Sources & evidence

ORD record
ord-fc5fbc4c4f054619ba4c19be2bcf32c4
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

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