Dichloromethane → HCID 117993526, compound

HRID 922586Notes

Reaction equation

HRID 922586 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:11][CH3:12])=[C:4]([CH3:13])[CH:3]=1.CC1(C)COB(B2OCC(C)(C)CO2)OC1.CC([O-])=O.[K+].ClCCl.Cl[C:39]1[N:44]=[C:43]([O:45][CH3:46])[C:42]([C@@:47]2([CH3:54])[CH2:52][CH2:51][CH2:50][NH:49][C:48]2=[O:53])=[CH:41][CH:40]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[CH2:11]([N:8]1[C:9]2[C:5](=[C:4]([CH3:13])[CH:3]=[C:2]([C:39]3[N:44]=[C:43]([O:45][CH3:46])[C:42]([C@@:47]4([CH3:54])[CH2:52][CH2:51][CH2:50][NH:49][C:48]4=[O:53])=[CH:41][CH:40]=3)[CH:10]=2)[CH:6]=[N:7]1)[CH3:12]

Participants

8

Reactant 6

HCID 6344Dichloromethane2×HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 74889420HCID 74889420, compoundHCID 117993132HCID 117993132, compound

Product 1

HCID 117993526HCID 117993526, compoundYield 94.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

An oven-dried 20 mL vial was charged with 6-bromo-1-ethyl-4-methyl-1H-indazole (345 mg, 1.4 mmol), 5,5,5′,5′-tetramethyl-2,2′-bi(1,3,2-dioxaborinane) (591 mg, 1.7 mmol), oven dried KOAc (566 mg, 5.8 mmol), anhydrous dioxane (5 mL) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropaladium(II) complex with dichloromethane (56.8 mg, 0.072 mmol). The mixture was bubbled with nitrogen gas for 5 minutes, and the reaction vial was sealed and heated at 110° C. for 1 h. After being cooled to r.t., to the reaction mixture was added (R)-3-(6-chloro-2-methoxypyridin-3-yl)-3-methylpiperidin-2-one (294 mg, 1.2 mmol), an aqueous solution of sodium carbonate (2M, 1.8 mL, 3.6 mmol) and additional [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (56.8 mg, 0.072 mmol). The reaction mixture was degassed with nitrogen, and heated at 100° C. for 75 min. The reaction mixture was cooled to r.t., diluted with EtOAc, filtered over Celite®, and the filtrate was concentrated. The crude residue was purified by silica gel column chromatography (0-10% EtOH/DCM, 40 g column) to afford (R)-3-(6-(1-ethyl-4-methyl-1H-indazol-6-yl)-2-methoxypyridin-3-yl)-3-methylpiperidin-2-one (429 mg, 79%) as an off-white solid. 1H NMR (600 MHz, CDCl3) δ 1.56 (t, 3H), 1.64-1.91 (m, 2H), 1.74 (s, 3H), 1.97-2.08 (m, 1H), 2.35-2.44 (m, 1H), 2.66 (s, 3H), 3.39-3.50 (m, 1H), 3.51-3.62 (m, 1H), 4.13 (s, 3H), 4.51 (q, 2H), 6.07 (brs, 1H), 7.43 (d, 1H), 7.55 (s, 1H), 7.68 (d, 1H), 7.89 (s, 1H), 8.01 (s, 1H). MS (AP+)(M+H) 379.

Workup

  1. customThe mixture was bubbled with nitrogen gas for 5 minutes
  2. customthe reaction
  3. customvial was sealed
  4. temperatureAfter being cooled to r.t., to the reaction mixture
  5. customThe reaction mixture was degassed with nitrogen
  6. temperatureheated at 100° C. for 75 min
  7. temperatureThe reaction mixture was cooled to r.t.
  8. additiondiluted with EtOAc
  9. filtrationfiltered over Celite®
  10. concentrationthe filtrate was concentrated
  11. customThe crude residue was purified by silica gel column chromatography (0-10% EtOH/DCM, 40 g column)

Sources & evidence

ORD record
ord-b378c37a3e0445398b17d5f95b6e758e
Source dataset
uspto-grants-2016_03
Patent number
US09278953B2

Reaction notes

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