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

HRID 1986239노트

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HRID 1986239 반응식
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

참가 물질

11

반응물 5

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

생성물 1

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

시약·촉매·용매 5

HCID 167845palladium(II) acetate촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 887Methanol용매HCID 6212Chloroform용매HCID 8028Tetrahydrofuran용매

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온도
-78 °C

실험 절차

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.

후처리

  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%

출처 및 근거

ORD 기록
ord-502d63a8c9184c2ba7e45983fdf60305
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07547691B2

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