Sodium Carbonate → HCID 59427346, compound

HRID 1042905Notes

Reaction equation

HRID 1042905 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[CH3:8].Cl[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([S:30][C:31]3[CH:36]=[CH:35][N:34]=[C:33]4[CH:37]=[C:38]([Si](C)(C)C)[O:39][C:32]=34)=[CH:26][CH:25]=2)=[N:15][N:14]=1.C(=O)([O-])[O-].[Na+].[Na+].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1(C)C=CC=CC=1.O.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:1][C:2]1[CH:3]=[C:4]([C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([S:30][C:31]4[CH:36]=[CH:35][N:34]=[C:33]5[CH:37]=[CH:38][O:39][C:32]=45)=[CH:26][CH:25]=3)=[N:15][N:14]=2)[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 27826743-Fluoro-4-methylbenzeneboronic acidHCID 86628671HCID 86628671, compound

Product 1

HCID 59427346HCID 59427346, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A microwave vial was charged with 3-fluoro-4-methylphenylboronic acid (0.058 g, 0.38 mmol), 4-chloro-N-(4-(2-(trimethylsilyl)furo[3,2-b]pyridin-7-ylthio)phenyl)phthalazin-1-amine (0.090 g, 0.19 mmol), and sodium carbonate (2.0 M in H2O) (0.38 ml, 0.75 mmol) and dissolved in toluene (1.5 mL) and water (0.2 mL). Pd(Ph3P)4 (0.011 g, 0.0094 mmol) was added and the reaction was microwaved at 200° C. for 30 minutes. The reaction was partitioned between water and DCM. The layers were separated and the aqueous layer was extracted twice with DCM. The combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was redissolved in 2 mL THF and TBAF (0.23 ml, 0.23 mmol) was added. The reaction was stirred at RT overnight. The reaction was concentrated and purified via Gilson HPLC (10-90% ACN:H2O). The clean fractions were partitioned between saturated sodium bicarbonate solution and DCM and the aqueous layer was extracted with DCM. The combined organic layers were dried with sodium sulfate, filtered, and concentrated to afford 4-(3-fluoro-4-methylphenyl)-N-(4-(furo[3,2-b]pyridin-7-ylthio)phenyl)phthalazin-1-amine as a light yellow solid. MS: M+H+=479.1

Workup

  1. customthe reaction was microwaved at 200° C. for 30 minutes
  2. customThe reaction was partitioned between water and DCM
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted twice with DCM
  5. dry with materialThe combined organic layers were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe material was redissolved in 2 mL THF
  9. concentrationThe reaction was concentrated
  10. custompurified via Gilson HPLC (10-90% ACN:H2O)
  11. customThe clean fractions were partitioned between saturated sodium bicarbonate solution and DCM
  12. extractionthe aqueous layer was extracted with DCM
  13. dry with materialThe combined organic layers were dried with sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-267d16e51f7e4b459c0bba453b470a98
Source dataset
uspto-grants-2013_10
Patent number
US08557816B2

Reaction notes

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