Sodium Carbonate → HCID 86652292, compound

HRID 1967443Notes

Reaction equation

HRID 1967443 reaction equation
FC(F)(F)S(O[C:7]1[CH:16]=[C:15]2[C:10]([C@H:11]([C:18]3[CH:27]=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:19]=3)[CH2:12][N:13]([CH3:17])[CH2:14]2)=[CH:9][CH:8]=1)(=O)=O.CN1C[C@@H](C2C=CC3C(=CC=CC=3)C=2)C2C(=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)C1.[Cl:60][C:61]1[N:62]=[N:63][C:64](Cl)=[CH:65][CH:66]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Cl:60][C:61]1[N:62]=[N:63][C:64]([C:7]2[CH:16]=[C:15]3[C:10]([C@H:11]([C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[CH:19]=4)[CH2:12][N:13]([CH3:17])[CH2:14]3)=[CH:9][CH:8]=2)=[CH:65][CH:66]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 673313,6-DichloropyridazineHCID 44546895HCID 44546895, compoundHCID 86652293HCID 86652293, compound

Product 1

HCID 86652292HCID 86652292, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of the crude Compound 10 (12.5 g, prepared from 15.1 g of Compound 9 using a similar procedure described earlier for the synthesis of Compound 10), 3,6-dichloropyridazine (5.60 g, 37.6 mmol), and sodium carbonate solution (40 mL. 2M, 80.0 mmol) in DMF (25 mL) was degassed with argon. To this mixture was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (2.6 g, 3.1 mmol). The resulting mixture was degassed with argon and then heated at 90° C. for 3 h. After cooling, the solution was quenched by adding water. The solution was extracted into dichloromethane (3×). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography (100:0 to 0:100 hexanes/ethyl acetate) provided the Compound 31 as a light-red solid (6.23 g, 51%); 1H NMR (500 MHz, CDCl3) δ 8.29 (d, J=9.0 Hz, 1H), 7.99 (d, J=9.0 Hz, 2H), 7.88-7.83 (m, 4H), 7.79 (s, 1H), 7.50-7.47 (m, 2H), 7.38 (dd, J=8.5, 1.5 Hz, 1H), 7.00 (d, J=0.8 Hz, 1H), 5.00-4.90 (m, 1H), 4.50-4.40 (m, 1H), 4.25-4.15 (m, 1H), 3.60-3.50 (m, 1H), 3.15-3.05 (m, 1H), 2.84 (s, 3H). ESI MS m/z 386 [M+H]+.

Workup

  1. customwas degassed with argon
  2. customThe resulting mixture was degassed with argon
  3. temperatureAfter cooling
  4. customthe solution was quenched
  5. additionby adding water
  6. extractionThe solution was extracted into dichloromethane (3×)
  7. dry with materialThe combined organic extracts were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by column chromatography (100:0 to 0:100 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-39b5fa0baa704ce7a71a1ce2be697d12
Source dataset
uspto-grants-2013_04
Patent number
US08420811B2

Reaction notes

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