Dichloromethane → HCID 117993077, compound

HRID 922585Notes

Reaction equation

HRID 922585 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:11])=[C:4]([Cl:12])[CH:3]=1.CC1(C)COB(B2OCC(C)(C)CO2)OC1.CC([O-])=O.[K+].ClCCl.Cl[C:38]1[N:43]=[C:42]([O:44][CH3:45])[C:41]([C@@:46]2([CH3:53])[CH2:51][CH2:50][CH2:49][NH:48][C:47]2=[O:52])=[CH:40][CH:39]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[Cl:12][C:4]1[CH:3]=[C:2]([C:38]2[N:43]=[C:42]([O:44][CH3:45])[C:41]([C@@:46]3([CH3:53])[CH2:51][CH2:50][CH2:49][NH:48][C:47]3=[O:52])=[CH:40][CH:39]=2)[CH:10]=[C:9]2[C:5]=1[CH:6]=[N:7][N:8]2[CH3:11]

Participants

8

Reactant 6

HCID 6344Dichloromethane2×HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 117993037HCID 117993037, compoundHCID 117993132HCID 117993132, compound

Product 1

HCID 117993077HCID 117993077, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

An oven dried vial was charged with 6-bromo-4-chloro-1-methyl-1H-indazole (507 mg, 2.1 mmol), 5,5,5′,5′-tetramethyl-2,2′-bi(1,3,2-dioxaborinane) (649 mg, 1.9 mmol), oven dried KOAc (604 mg, 6.2 mmol), [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (54 mg, 0.066 mmol) and dioxane (10 mL), and purged with nitrogen for 20 min. The reaction was heated at 100° C. for 1 h. The mixture was filtered through a pad of Celite®, and the filter cake was rinsed with dioxane. The filtrate was concentrated under reduced pressure to afford the crude residue (530 mg). To a solution of this crude residue (370 mg) in degassed dioxane (2 mL) was added (R)-3-(6-chloro-2-methoxypyridin-3-yl)-3-methylpiperidin-2-one (300 mg, 1.2 mmol), an aqueous solution of sodium carbonate (2 M, 1.5 mL, 2.9 mmol) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (54 mg, 0.066 mmol). The reaction mixture was degassed with nitrogen, and heated at 100° C. for 1 h. The reaction mixture was cooled to r.t., and anhydrous Na2SO4 was added. The mixture was filtered through a pad of Celite®, and the filter cake was rinsed with dioxane. The filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (0-100% EtOAc in Heptane to 0-30% EtOH/DCM) to afford (R)-3-(6-(4-chloro-1-methyl-1H-indazol-6-yl)-2-methoxypyridin-3-yl)-3-methylpiperidin-2-one (358 mg, 79%). 1H NMR (600 MHz, CDCl3) δ 1.68 (d, 1H), 1.74 (s, 3H), 1.88 (d, 1H), 1.97-2.07 (m, 1H), 2.39 (td, 1H), 3.37-3.47 (m, 1H), 3.50-3.60 (m, 1H), 4.12 (s, 3H), 4.15 (s, 3H), 5.81 (brs, 1H), 7.42 (d, 1H), 7.70 (d, 1H), 7.82 (s, 1H), 7.94 (s, 1H), 8.06 (s, 1H). MS (AP+)(M+H) 385.

Workup

  1. customAn oven dried vial
  2. custompurged with nitrogen for 20 min
  3. filtrationThe mixture was filtered through a pad of Celite®
  4. washthe filter cake was rinsed with dioxane
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customto afford the crude residue (530 mg)
  7. customThe reaction mixture was degassed with nitrogen
  8. temperatureheated at 100° C. for 1 h
  9. temperatureThe reaction mixture was cooled to r.t.
  10. additionanhydrous Na2SO4 was added
  11. filtrationThe mixture was filtered through a pad of Celite®
  12. washthe filter cake was rinsed with dioxane
  13. concentrationThe filtrate was concentrated under reduced pressure
  14. customThe crude product was purified by silica gel column chromatography (0-100% EtOAc in Heptane to 0-30% EtOH/DCM)

Sources & evidence

ORD record
ord-d2a0dc0537644e78b41de49ec2c1075e
Source dataset
uspto-grants-2016_03
Patent number
US09278953B2

Reaction notes

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