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

HRID 1986863

反応式

HRID 1986863 の反応式
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

参加物

11

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 5

HCID 24290Palladium Chloride触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-1d2fc3dece8f447082dd2df7c01c5557
出典データセット
uspto-grants-2009_06
特許番号
US07550470B2

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