Sodium Carbonate → Ethyl 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]nicotinate

HRID 1986863

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HRID 1986863 반응식
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+].I[C:37]1[CH:38]=[N:39][N:40]2[CH:45]=[C:44]([C:46]3[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=3)[CH:43]=[N:42][C:41]=12.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.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].Cl[Pd]Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[CH3:53][O:52][C:49]1[CH:48]=[CH:47][C:46]([C:44]2[CH:43]=[N:42][C:41]3[N:40]([N:39]=[CH:38][C:37]=3[C:2]3[CH:3]=[N:4][CH:5]=[C:6]([CH:12]=3)[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:45]=2)=[CH:51][CH:50]=1

참가 물질

11

반응물 5

HCID 10340Sodium CarbonateHCID 140785Ethyl 5-bromopyridine-3-carboxylateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 577226133-Iodo-6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine

생성물 1

HCID 57722617Ethyl 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]nicotinate

시약·촉매·용매 5

HCID 24290Palladium Chloride촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

A mixture of ethyl 5-bromonicotinate (500 mg, 2.17 mmol, 1 equiv), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (662 mg, 2.61 mmol, 1.20 equiv), potassium acetate (639 g, 6.51 mmol, 3.00 equiv), and 1,1′-bis (diphenylphophino)-ferrocene)dichloropalladium (89 mg, 0.11 mmol, 0.050 equiv) in DMF (5 mL) was heated at 80° C. for 16 hours. The mixture was partitioned between water (100 mL) and ethyl acetate (2×50 mL). The organic layer was dried over sodium sulfate and concentrated. A solution of the residue, 3-iodo-6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine (2-1, 254 mg, 0.723 mmol, 0.333 equiv), tetrakis(triphenylphosphine)palladium (50 mg, 0.043 mmol, 0.020 equiv) in a mixture of aqueous 2M sodium carbonate solution (1 mL) and dioxane (10 mL) was heated at reflux for 16 hours. The reaction was then partitioned between water (50 mL) and ethyl acetate (2×50 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was suspended in methanol and filtered to give ethyl 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]nicotinate (2-2) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 9.50 (d, 1H, J=2.2 Hz), 9.12 (d, 1H, J=2.2 Hz), 8.96 (t, 1H, J=2.2 Hz), 8.88 (d, 1H, J=2.2 Hz), 8.8.3 (d, 1H, J=2.4 Hz), 8.54 (s, 1H), 7.56 (d, 2H, J=8.8 Hz), 7.08 (d, 2H, J=8.8 Hz), 4.48 (q, 2H, J=7.3 Hz), 3.90 (s, 3H), 1.46 (t, 3H, J=7.1 Hz).

후처리

  1. customThe mixture was partitioned between water (100 mL) and ethyl acetate (2×50 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. temperaturewas heated
  5. temperatureat reflux for 16 hours
  6. customThe reaction was then partitioned between water (50 mL) and ethyl acetate (2×50 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated
  9. filtrationfiltered

출처 및 근거

ORD 기록
ord-1d2fc3dece8f447082dd2df7c01c5557
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07550470B2

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