Sodium Carbonate → HCID 66743166, compound

HRID 449725Notes

Reaction equation

HRID 449725 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:27]=[CH:26][CH:25]=[C:24](B3OC(C)(C)C(C)(C)O3)[C:18]=1[CH2:19][O:20][C:21](=[O:23])[CH3:22])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].Cl[C:44]1[CH:45]=[C:46]([Si:52]([CH3:55])([CH3:54])[CH3:53])[C:47](=[O:51])[N:48]([CH3:50])[N:49]=1.IC1C=C([Si](C)(C)C)C(=O)N(C)N=1>>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([C:44]3[CH:45]=[C:46]([Si:52]([CH3:54])([CH3:53])[CH3:55])[C:47](=[O:51])[N:48]([CH3:50])[N:49]=3)[C:18]=1[CH2:19][O:20][C:21](=[O:23])[CH3:22])[N:9]=[CH:8]2)([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 4

HCID 10340Sodium CarbonateHCID 594737692-(6-(tert-Butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetateHCID 66742985HCID 66742985, compoundHCID 66743378HCID 66743378, compound

Product 1

HCID 66743166HCID 66743166, compoundYield 71%

Procedure

In round bottom flask was placed 3.21 g acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester, 2.06 g sodium carbonate, 0.68 g bistriphenylphosphine palladium dichloride, and 1.99 g a 6:4 mixture of 6-chloro-2-methyl-4-trimethylsilanyl-2H-pyridazin-3-one and 6-iodo-2-methyl-4-trimethylsilanyl-2H-pyridazin-3-one followed by 130 mL of dioxane (EM DriSolv)-water (10:1). The mixture was vacuum flushed 5× argon, then set in a bath at 95° C. and stirred (mechanical). After 5.5 hours, the mixture was cooled, taken up in 350 mL of ethyl acetate and washed 1×75 mL of brine. The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (Silicycle 120 g, 3.5×21.5 cm, 207 vol), applied in dichloromethane eluting with CH2Cl2-ethyl acetate (80:20), followed by chromatography on silica gel (Silicycle 120 g, 3.5×21.5 cm, 207 vol), applied in dichloromethane, eluting with dichloromethane-ethyl acetate (80:20) afforded 2.5418 g (71%) of product as a foam.

Workup

  1. customIn round bottom flask was placed
  2. customflushed 5× argon
  3. customset in a bath at 95° C.
  4. temperaturethe mixture was cooled
  5. washwashed 1×75 mL of brine
  6. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by chromatography on silica gel (Silicycle 120 g, 3.5×21.5 cm, 207 vol)
  10. washeluting with dichloromethane-ethyl acetate (80:20)

Sources & evidence

ORD record
ord-622f2d5b491944fc80066c728d897377
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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