Sodium Carbonate → HCID 59508402, compound

HRID 1095415Notes

Reaction equation

HRID 1095415 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([S:11]([CH2:14][CH2:15][CH2:16][O:17][Si](C(C)C)(C(C)C)C(C)C)(=[O:13])=[O:12])([CH3:10])[CH3:9])[CH:5]=[C:4]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][C@@H:29]2[CH3:34])[N:3]=1.CC1(C)C(C)(C)OB([C:43]2[CH:49]=[CH:48][C:46]([NH2:47])=[CH:45][CH:44]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C.C(Cl)Cl.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.C(O)C.O.COCCOC.CN(C=O)C>[NH2:47][C:46]1[CH:48]=[CH:49][C:43]([C:2]2[N:7]=[C:6]([C:8]([S:11]([CH2:14][CH2:15][CH2:16][OH:17])(=[O:12])=[O:13])([CH3:10])[CH3:9])[CH:5]=[C:4]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][C@@H:29]3[CH3:34])[N:3]=2)=[CH:44][CH:45]=1

Participants

12

Reactant 4

HCID 10340Sodium CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 59508396HCID 59508396, compound

Product 1

HCID 59508402HCID 59508402, compoundYield 61.5%

Reagents, catalysts & solvents 7

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Bis(triphenylphosphine)palladium(II) chloride (0.176 g, 0.25 mmol) was added to 3-[2-[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-ylsulfonyl]propoxy-tri(propan-2-yl)silane (2 g, 3.74 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.107 g, 5.05 mmol) and 2M sodium carbonate solution (3 mL, 6.00 mmol) in a solvent mixture of DMF (5 mL), DME (8 mL), water (2 mL) and ethanol (1.5 mL) and the resulting mixture stirred at 90° C. for 5 hours, under an inert atmosphere. The reaction mixture was diluted with ethyl acetate (200 mL), and washed with water (2×100 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford a residue which was dissolved in DCM (100 mL), and tetrabutylammonium fluoride (18.72 mL, 18.72 mmol) added. The mixture was stirred at RT for 2 hours. The reaction mixture was diluted with DCM (100 mL), and washed sequentially with a saturated aqueous solution of ammonium chloride (50 mL) and water (2×100 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20 to 100% ethyl acetate in isohexane then 4% methanol in ethyl acetate, to give a material which was further purified by ion exchange chromatography using an SCX column, eluting with 7N ammonia in methanol, to give the desired material as a beige solid (1.0 g).

Workup

  1. washwashed with water (2×100 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford a residue which
  6. stirringThe mixture was stirred at RT for 2 hours
  7. washwashed sequentially with a saturated aqueous solution of ammonium chloride (50 mL) and water (2×100 mL)
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customto afford crude product
  12. customThe crude product was purified by flash silica chromatography, elution gradient 20 to 100% ethyl acetate in isohexane
  13. custom4% methanol in ethyl acetate, to give a material which
  14. customwas further purified by ion exchange chromatography
  15. washeluting with 7N ammonia in methanol

Sources & evidence

ORD record
ord-5aa71655d77243cbb3cd10b8b2ea0092
Source dataset
uspto-grants-2012_03
Patent number
US08138183B2

Reaction notes

Loading…