Dimethylformamide → HCID 69101861, compound

HRID 1809163Notes

Reaction equation

HRID 1809163 reaction equation
Br[N:2]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([NH2:5])=[O:4].N1[CH:18]=[C:17](B(O)O)[CH:16]=[N:15][CH:14]=1.[CH3:22]N(C=O)C.CCN(CC)CC>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:15]1[CH:14]=[CH:22][CH:18]=[CH:17][C:16]=1[N:2]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([NH2:5])=[O:4]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 86619756HCID 86619756, compound

Product 1

HCID 69101861HCID 69101861, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a 15 mL pressure vessel was added 42 (250 mg, 0.594 mmol, 1.0 eq.), 5-pyrimidine boronic acid (74 mg, 0.594 mmol, 1.0 eq.), PdCl2(dppf)2 (43 mg, 0.0594 mmol, 0.1 eq.), DMF (5 mL), and Et3N (166 μL, 1.19 mmol, 2.0 eq.). The vessel was sealed and heated at 90° C. overnight upon which the reaction mixture turned from dark red to black. The reaction mixture was cooled and then diluted with EtOAc (100 mL) and the organic phase was washed with 10% aq LiCl (3×50 mL), and brine (50 mL). The combined aqueous phases were extracted with EtOAc (50 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated to give a black oil. The crude material was purified via flash chromatography (30% to 70% EtOAc/Hex) to give a white powder (32 mg, 10%). 1H-NMR, Varian 400 MHz, (DMSO-d6) δ 9.38 (s, 1H), 9.18 (s, 1H), 9.10 (s, 1H), 8.78 (s, 1H), 8.17 (s, 1H), 7.93 (s, 1H), 7.56 (d, 1H), 7.40 (t, 1H), 7.24 (m, 2H), 7.00 (d, 1H), 3.17 (s, 3H) ppm.

Workup

  1. customThe vessel was sealed
  2. temperatureThe reaction mixture was cooled
  3. washthe organic phase was washed with 10% aq LiCl (3×50 mL), and brine (50 mL)
  4. extractionThe combined aqueous phases were extracted with EtOAc (50 mL)
  5. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a black oil
  9. customThe crude material was purified via flash chromatography (30% to 70% EtOAc/Hex)

Sources & evidence

ORD record
ord-b692872641634d67b98bad6bbd95cfab
Source dataset
uspto-grants-2013_01
Patent number
US08362017B2

Reaction notes

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