Sodium Carbonate → HCID 67480116, compound

HRID 509553Notes

Reaction equation

HRID 509553 reaction equation
[C:1]([O:5][C:6]([N:8]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C:9]1[C:14]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:22][C:21]=3[F:36])[CH:16]=2)=[CH:13][C:12](B2OC(C)(C)C(C)(C)O2)=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:54]1[CH:59]=[CH:58][C:57]([S:60]([CH:63]([CH3:65])[CH3:64])(=[O:62])=[O:61])=[CH:56][N:55]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:49]([O:48][C:46]([N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:9]1[C:14]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[CH:22][C:21]=3[F:36])[CH:16]=2)=[CH:13][C:12]([C:54]2[CH:59]=[CH:58][C:57]([S:60]([CH:63]([CH3:65])[CH3:64])(=[O:61])=[O:62])=[CH:56][N:55]=2)=[CH:11][N:10]=1)=[O:47])([CH3:51])([CH3:50])[CH3:52]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 529881802-Bromo-5-(propane-2-sulfonyl)pyridineHCID 68088998HCID 68088998, compound

Product 1

HCID 67480116HCID 67480116, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of tert-butyl N-[[4-[5-[2-[bis(tert-butoxycarbonyl)amino]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridyl]isoxazol-3-yl]-3-fluoro-phenyl]methyl]-N-methyl-carbamate (322.6 mg, 0.3339 mmol) and 2-bromo-5-isopropylsulfonyl-pyridine (105.8 mg, 0.4007 mmol) in DMF (3 mL) was degassed and placed under an atmosphere of nitrogen. Pd(PPh3)2Cl2 (13.81 mg, 0.03339 mmol) was added and the reaction again degassed. 2M aqueous Na2CO3 (501.0 μL, 1.002 mmol) was added and the reaction was stirred at 95° C. for 2 hours. The reaction mixture was partitioned between EtOAc and brine and the aqueous layer extracted with EtOAc (×3). The combined organic extracts were washed with water (×3) and brine (×2), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 40 g column, loading with DCM and eluting with 0 to 50% EtOAc/Petroleum Ether) to give the impure sub-title compound as a yellow oil which was used in the next step without purification.

Workup

  1. customwas degassed
  2. customthe reaction
  3. customagain degassed
  4. customThe reaction mixture was partitioned between EtOAc and brine
  5. extractionthe aqueous layer extracted with EtOAc (×3)
  6. washThe combined organic extracts were washed with water (×3) and brine (×2)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography (ISCO Companion™, 40 g column, loading with DCM and eluting with 0 to 50% EtOAc/Petroleum Ether)

Sources & evidence

ORD record
ord-8b2fe2be0a6c43148927c9dbc66b70cf
Source dataset
uspto-grants-2015_08
Patent number
US09096584B2

Reaction notes

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