Sodium Carbonate → 2,5-Dichloro-4-(7-methoxybenzo[b]thiophen-2-yl)-pyrimidine

HRID 1986239Notes

Reaction equation

HRID 1986239 reaction equation
C([Li])CCC.[CH3:6][O:7][C:8]1[C:13]2[S:14][CH:15]=[CH:16][C:12]=2[CH:11]=[CH:10][CH:9]=1.B(OC(C)C)(OC(C)C)OC(C)C.C([O-])([O-])=O.[Na+].[Na+].[Cl:36][C:37]1[N:42]=[C:41](Cl)[C:40]([Cl:44])=[CH:39][N:38]=1>C1COCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)(Cl)Cl.CO>[Cl:36][C:37]1[N:42]=[C:41]([C:15]2[S:14][C:13]3[C:8]([O:7][CH3:6])=[CH:9][CH:10]=[CH:11][C:12]=3[CH:16]=2)[C:40]([Cl:44])=[CH:39][N:38]=1

Participants

11

Reactant 5

HCID 10340Sodium CarbonateHCID 21531Triisopropyl borateHCID 2372592,4,5-TrichloropyrimidineHCID 110842177-Methoxybenzo[b]thiopheneHCID 178418339Butyllithium

Product 1

HCID 866253692,5-Dichloro-4-(7-methoxybenzo[b]thiophen-2-yl)-pyrimidine

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 887MethanolSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (4.19 mL, 1.6 M in hexane) is added dropwise over 1 hour to a stirred solution of 7-methoxy-benzo[b]thiophene (1.00 g, 6.09 mmol) and triisopropyl borate (1.26 g, 6.70 mmol) in anhydrous THF (10 mL) at −78° C. under nitrogen. The resultant mixture is allowed to stir at −78° C. for 30 minutes, then at −20° C. for another 30 minutes. Aqueous Na2CO3 solution (2 M, 6.09 mL) is added to the mixture, followed by the addition of 1,1′-bis(diphenylphosphino)ferrocene (169 mg, 0.304 mmol), palladium(II) acetate (68.3 mg, 0.304 mmol) and 2,4,5-trichloropyrimidine (1.12 g, 6.09 mmol). Then the reaction mixture is heated to reflux for 18 hours. At ambient temperature CH3OH (10 mL) and CHCl3 (90 mL) are added to the mixture. The organic layer is separated, dried over MgSO4, filtered, and concentrated. After chromatographic purification on silica gel eluting with CH3OH in dichloromethane 0-1%, the title compound is obtained as a yellowish solid (40 mg) and 872 mg starting 7-methoxy-benzo[b]thiophene is recovered.

Workup

  1. waitat −20° C. for another 30 minutes
  2. temperatureThen the reaction mixture is heated
  3. temperatureto reflux for 18 hours
  4. customThe organic layer is separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customAfter chromatographic purification on silica gel eluting with CH3OH in dichloromethane 0-1%

Sources & evidence

ORD record
ord-502d63a8c9184c2ba7e45983fdf60305
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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