Isopropanol → HCID 86707517, compound

HRID 339021Notes

Reaction equation

HRID 339021 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:12]3[N:16]4[CH:17]=[C:18]([C@@H:21]([N:26]5[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:27]5)[C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:20][C:15]4=[N:14][N:13]=3)=[N:9]2)=[CH:4][C:3]=1[F:39].[CH3:40][N:41]1[C:45](B2OC(C)(C)C(C)(C)O2)=[CH:44][C:43]([CH3:55])=[N:42]1.[F-].[Cs+].CC(O)C.C(N(CC)CC)C>C(OCC)(=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]>[CH3:40][N:41]1[C:45]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[CH:7][C:8]([C:12]4[N:16]5[CH:17]=[C:18]([C@@H:21]([N:26]6[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:27]6)[C:22]([F:24])([F:25])[F:23])[CH:19]=[CH:20][C:15]5=[N:14][N:13]=4)=[N:9]3)=[CH:4][C:3]=2[F:39])=[CH:44][C:43]([CH3:55])=[N:42]1

Participants

8

Reactant 5

HCID 3776IsopropanolHCID 8471TriethylamineHCID 25953Cesium fluorideHCID 49127481,3-DIMETHYL-5-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)-1H-PYRAZOLEHCID 86707518HCID 86707518, compound

Product 1

HCID 86707517HCID 86707517, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl (S)-1-((R)-1-(3-(7-bromo-6-fluoro quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)pyrrolidin-3-ylcarbamate (0.10 g, 0.16 mmol), 1,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.073 g, 0.33 mmol) and cesium fluoride (0.065 g, 0.43 mmol) in 2-propanol (3.3 mL, 0.16 mmol) was degassed with nitrogen. Maintaining a nitrogen atmosphere, triethylamine (0.034 mL, 0.25 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.013 g, 0.016 mmol) were added, and the vessel sealed and heated at 100° C. for 17 hours. After cooling, the reaction mixture was diluted with ethyl acetate (10 mL), filtered through a plug of Celite®, and concentrated under reduced pressure. Purification of the residue by reverse phase chromatography on a C18 column (0-100% acetonitrile/water) provided the title compound (0.074 g, 72%).

Workup

  1. customwas degassed with nitrogen
  2. additionwere added
  3. customthe vessel sealed
  4. temperatureAfter cooling
  5. filtrationfiltered through a plug of Celite®
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the residue by reverse phase chromatography on a C18 column (0-100% acetonitrile/water)

Sources & evidence

ORD record
ord-9d98199c0730446eaee034056759c44a
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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