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

HRID 1986863

Reaction equation

HRID 1986863 reaction equation
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

Participants

11

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 5

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-1d2fc3dece8f447082dd2df7c01c5557
Source dataset
uspto-grants-2009_06
Patent number
US07550470B2

Linked notes

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