Sodium Carbonate → 2-[Bis(tert-butoxycarbonyl)amino]-5-(2'-methylthiophenyl)pyrimidine

HRID 610126Notes

Reaction equation

HRID 610126 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9]1[N:14]=[CH:13][C:12](Br)=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23][S:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[C:1]([O:5][C:6]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9]1[N:14]=[CH:13][C:12]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[S:24][CH3:23])=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27735432-(Methylthio)benzeneboronic acidHCID 11977091tert-butyl N-(5-bromopyrimidin-2-yl)-N-((tert-butoxy)carbonyl)carbamate

Product 1

HCID 181773202-[Bis(tert-butoxycarbonyl)amino]-5-(2'-methylthiophenyl)pyrimidineYield 96.3%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 241BenzeneSolvent

Procedure

2-[Bis(tert-butoxycarbonyl)amino]-5-bromopyrimidine (2.00 g, 5.3 mmol) was dissolved in benzene (130 mL). 2-methylthiophenylboronic acid (2.24 g, 13.3 mmol), aq. sodium carbonate (13 mL, 2.0 M, 26 mmol), tetrabutyl ammonium bromide (86 mg, 0.26 mmol), and bis(triphenylphosphine)palladium(II)chloride (190 mg, 0.27 mmol) were added, and the resulting mixture was first purged with vacuum and argon, then refluxed 17 hours. The cooled mixture was diluted with EtOAc and water. The layers were separated, and the organic was dried over Na2SO4, filtered, and evaporated. The crude product was chromatographed on silica gel (50% EtOAc/hexanes), evaporated, and chromatographed a second time on silica gel (30-50% EtOAc/hexanes) to yield the desired product (2.13 g, 96%). 1H NMR (CDCl3): δ8.81 (s, 2H) , 7.41 (m, 2H) , 7.25 (m, 2H) , 2.39 (s, 3H), 1.49 (s, 18H).

Workup

  1. customthe resulting mixture was first purged with vacuum and argon
  2. temperaturerefluxed 17 hours
  3. additionThe cooled mixture was diluted with EtOAc and water
  4. customThe layers were separated
  5. dry with materialthe organic was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was chromatographed on silica gel (50% EtOAc/hexanes)
  9. customevaporated
  10. customchromatographed a second time on silica gel (30-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8f82250f3e6b46f1be227e7a0ed79668
Source dataset
uspto-grants-1999_12
Patent number
US05998424

Reaction notes

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