Sodium Carbonate → HCID 117992734, compound

HRID 922588Notes

Reaction equation

HRID 922588 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C@@:10]2([CH3:17])[CH2:15][CH2:14][CH2:13][NH:12][C:11]2=[O:16])=[CH:4][CH:3]=1.[CH3:18][N:19]1[C:27]2[C:22](=[CH:23][C:24](B(O)O)=[CH:25][CH:26]=2)[CH:21]=[CH:20]1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O1CCOCC1>[CH3:9][O:8][C:6]1[C:5]([C@@:10]2([CH3:17])[CH2:15][CH2:14][CH2:13][NH:12][C:11]2=[O:16])=[CH:4][CH:3]=[C:2]([C:24]2[CH:23]=[C:22]3[C:27](=[CH:26][CH:25]=2)[N:19]([CH3:18])[CH:20]=[CH:21]3)[N:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27598671-Methyl-1H-indole-5-boronic acidHCID 117993132HCID 117993132, compound

Product 1

HCID 117992734HCID 117992734, compoundYield 94%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

To a large microwave vial was added (R)-3-(6-chloro-2-methoxypyridin-3-yl)-3-methylpiperidin-2-one (1.20 g, 4.7 mmol), 1-methyl-1H-indol-5-ylboronic acid (0.82 g, 4.7 mmol), dioxane (10 mL), 2 M Na2CO3 (5.9 mL, 11.8 mmol), and PdCl2(dppf) CH2Cl2 (193 mg, 0.236 mmol). Nitrogen gas was bubbled through the reaction mixture for 5 minutes prior to sealing the vessel. The reaction was stirred for 18 h at 105° C. The mixture was cooled to r.t., diluted with ethyl acetate, and filtered over Celite®. The filtrate was concentrated to a brown paste. Purification by column chromatography (80 g RediSep Gold column) with a 0-10% EtOH/DCM gradient provided (R)-3-(2-methoxy-6-(1-methyl-1H-indol-5-yl)pyridin-3-yl)-3-methylpiperidin-2-one (1.54 g, 94%) as a light orange solid. 1H NMR (600 MHz, CDCl3) δ: 1.62-1.69 (m, 1H), 1.72 (s, 3H), 1.77-1.86 (m, 1H), 1.93-2.03 (m, 1H), 2.39 (td, 1H), 3.36-3.44 (m, 1H), 3.52 (td, 1H), 3.82 (s, 3H), 4.11 (s, 3H), 6.16 (br s., 1H), 6.56 (d, 1H), 7.07 (d, 1H), 7.36 (d, 1H), 7.38 (d, 1H), 7.62 (d, 1H), 7.93 (dd, 1H), 8.29 (s, 1H); MS (ES+)(M+H) 350.

Workup

  1. customNitrogen gas was bubbled through the reaction mixture for 5 minutes
  2. temperatureThe mixture was cooled to r.t.
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered over Celite®
  5. concentrationThe filtrate was concentrated to a brown paste
  6. customPurification by column chromatography (80 g RediSep Gold column) with a 0-10% EtOH/DCM gradient

Sources & evidence

ORD record
ord-2e0afadd87ca4b1492987f0b254b74ed
Source dataset
uspto-grants-2016_03
Patent number
US09278953B2

Reaction notes

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