Sodium Carbonate → HCID 15603657, compound

HRID 2250358Notes

Reaction equation

HRID 2250358 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:24](=[O:25])[N:11]3[N:12]=[C:13](Cl)[C:14]([C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=4)=[CH:15][C:10]3=[N:9]2)=[CH:5][CH:4]=1.[Cl:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.C([O-])([O-])=O.[Na+].[Na+]>O.C1(C)C=CC=CC=1.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>[F:28][C:2]([F:29])([F:1])[C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:24](=[O:25])[N:11]3[N:12]=[C:13]([C:34]4[CH:35]=[CH:36][C:31]([Cl:30])=[CH:32][CH:33]=4)[C:14]([C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=4)=[CH:15][C:10]3=[N:9]2)=[CH:5][CH:4]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 58772594HCID 58772594, compound

Product 1

HCID 15603657HCID 15603657, compoundYield 13%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
125 °C

Procedure

To a suspension of 2-(4-(trifluoromethyl)benzyl)-6-chloro-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (150 mg, 0.34 mmol), 4-chlorophenylboronic acid (60 mg, 0.38 mmol), Na2CO3 (90 mg, 0.85 mmol) dissolved in water (0.2 mL) in toluene (3 mL) was added Pd(PPh3)4 (25 mg, 0.02 mmol). The resulting reaction mixture was bubbled with argon for 10 min before the flask was placed in an oil bath preheated at 125° C. After stirring at 125° C. for 10 h, the reaction was then allowed to cool to room temperature. To the reaction was added water (10 mL), the aqueous mixture extracted with EtOAc (10 mL×3). The combined EtOAc extracts were washed with water (10 mL×2), followed by saturated aqueous NaCl (10 mL×2) and concentrated under reduced pressure. The crude product was purified by reverse phase preparative HPLC (Conditions: Phenomenex Luna 5μ C18 21.2×100 mm; Eluted with 17% to 100% B, 25 min gradient, hold at 100% B for 5 min (A=90% H2O, 10% acetonitrile and B=10% H2O, 90% acetonitrile); Flow rate at 20 mL/min, UV detection at 220 nm) to obtain 22 mg (13%) the title compound as a yellow solid. LC/MS (Method C): retention time=4.26 min; (M+H)+=515. 1H NMR (CDCl3, 500 MHz): δ 7.61 (d,J=5.0 Hz, 2H), 7.56 (d,J=5.0 Hz, 2H), 7.41(s, 1H), 7.24-7.30 (m, 4H), 7.21 (d,J=5.0 Hz, 2H,), 7.01 (d,J=5.0 Hz, 2H), 5.29 (s, 2H).

Workup

  1. customThe resulting reaction mixture
  2. customwas bubbled with argon for 10 min before the flask
  3. customwas placed in an oil bath
  4. custompreheated at 125° C
  5. temperatureto cool to room temperature
  6. additionTo the reaction was added water (10 mL)
  7. extractionthe aqueous mixture extracted with EtOAc (10 mL×3)
  8. washThe combined EtOAc extracts were washed with water (10 mL×2)
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by reverse phase preparative HPLC (Conditions
  11. washEluted with 17% to 100% B, 25 min gradient
  12. waithold at 100% B for 5 min

Sources & evidence

ORD record
ord-107d8ef2fea74a2e97dd579d9a81b83d
Source dataset
uspto-grants-2008_01
Patent number
US07317012B2

Reaction notes

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