Ethanol → HCID 59508406, compound

HRID 1095414Notes

Reaction equation

HRID 1095414 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:15]2[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][CH:16]=2)O1.[C:23]1([S:29]([C:32]([C:35]2[CH:40]=[C:39]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][C@@H:42]3[CH3:47])[N:38]=[C:37](Cl)[N:36]=2)([CH3:34])[CH3:33])(=[O:31])=[O:30])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(O)C>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.CN(C=O)C>[C:23]1([S:29]([C:32]([C:35]2[CH:40]=[C:39]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][C@@H:42]3[CH3:47])[N:38]=[C:37]([C:15]3[CH:16]=[CH:17][C:18]([NH2:19])=[CH:20][CH:21]=3)[N:36]=2)([CH3:34])[CH3:33])(=[O:31])=[O:30])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

9

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 59508391HCID 59508391, compound

Product 1

HCID 59508406HCID 59508406, compoundYield 71.3%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Sodium carbonate (2M aqueous solution) (3.21 mL, 6.43 mmol) was added to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (391 mg, 1.79 mmol) and 4-[2-(benzenesulfonyl)propan-2-yl]-2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine (707 mg, 1.79 mmol) in a mixture of DME (8.0 mL), ethanol (4.0 mL), DMF (4.0 mL) and water (4.0 mL) under nitrogen. The mixture was degassed and purged with nitrogen three times. Bis(triphenylphosphine)palladium(II) chloride (63 mg, 0.09 mmol) was added and the mixture was degassed and purged with nitrogen a further three times. The resulting suspension was stirred at 80° C. for 30 minutes. The reaction mixture was concentrated and diluted with ethyl acetate (50 mL), and washed sequentially with water (2×25 mL) and saturated brine (25 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 2% methanol in DCM, to give the desired material as a beige solid (578 mg).

Workup

  1. customThe mixture was degassed
  2. custompurged with nitrogen three times
  3. customthe mixture was degassed
  4. custompurged with nitrogen a further three times
  5. concentrationThe reaction mixture was concentrated
  6. additiondiluted with ethyl acetate (50 mL)
  7. washwashed sequentially with water (2×25 mL) and saturated brine (25 mL)
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customto afford crude product
  12. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 2% methanol in DCM

Sources & evidence

ORD record
ord-6a94772a30754ac9ab1fdb62b9eae273
Source dataset
uspto-grants-2012_03
Patent number
US08138183B2

Reaction notes

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