Toluene → HCID 89573714, compound

HRID 1911039Notes

Reaction equation

HRID 1911039 reaction equation
Br[C:2]1[CH:23]=[C:22]2[C:5]([CH2:6][CH2:7][C@@H:8]3[CH2:13][S:12][C:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[N:10][C@@:9]32[CH3:24])=[CH:4][CH:3]=1.[NH:25]1[CH:29]=[C:28](B(O)O)[CH:27]=[N:26]1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+]>C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe].O.O1CCOCC1>[CH3:24][C@@:9]12[C:22]3[C:5](=[CH:4][CH:3]=[C:2]([C:28]4[CH:29]=[N:25][NH:26][CH:27]=4)[CH:23]=3)[CH2:6][CH2:7][C@@H:8]1[CH2:13][S:12][C:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:18])[CH3:19])=[N:10]2

Participants

9

Reactant 5

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 177502781H-Pyrazole-4-boronic acidHCID 71084845HCID 71084845, compound

Product 1

HCID 89573714HCID 89573714, compound

Reagents, catalysts & solvents 3

HCID 178477754HCID 178477754, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Dioxane (1 mL) and water (0.1 mL) were added to a mixture of tert-butyl rel-((4aS,10bS)-9-bromo-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate from preparation C (10 mg, 0.024 mmol), (1H-pyrazol-4-yl)boronic acid (27.2 mg, 0.243 mmol) and potassium carbonate (33.6 mg, 0.243 mmol). Nitrogen was bubbled through the mixture for 5 min. 1,1′-Bis(diphenylphosphino)ferrocenepalladium (II) dichloride, toluene (10 mg, 0.012 mmol) was added and the resulting mixture was heated at 100° C. for 1 h. The reaction contents were cooled to rt and were transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (10 mL). The aqueous layer was extracted with EtOAc (3×25 mL). The combined organic layers were washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated. The crude product of step 19A was used in the next step without further purification. LCMS (M+H)+=399.08.

Workup

  1. customNitrogen was bubbled through the mixture for 5 min
  2. customThe reaction contents
  3. temperaturewere cooled to rt
  4. customwere transferred to a separatory funnel
  5. extractionThe aqueous layer was extracted with EtOAc (3×25 mL)
  6. washThe combined organic layers were washed with brine (10 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product of step 19A was used in the next step without further purification

Sources & evidence

ORD record
ord-15c887f919dc4b69bc76b4d0cacaa1a2
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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