Sodium Carbonate → HCID 117993113, compound

HRID 922587Notes

Reaction equation

HRID 922587 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][CH:24]=[C:25](B3OC(C)(C)C(C)(C)O3)[CH:26]=2)[CH:21]=[CH:20]1.O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.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]>[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:25]2[CH:26]=[C:27]3[C:22]([CH:21]=[CH:20][N:19]3[CH3:18])=[CH:23][CH:24]=2)[N:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 185257691-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 117993132HCID 117993132, compound

Product 1

HCID 117993113HCID 117993113, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a vessel containing (R)-3-(6-chloro-2-methoxypyridin-3-yl)-3-methylpiperidin-2-one (80 mg, 0.31 mmol), 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (105 mg, 0.41 mmol), dioxane (3 mL), and 2 M Na2CO3 (0.31 mL, 0.63 mmol) was added Pd(dppf)Cl2 (23 mg, 0.031 mmol). The reaction was stirred for 18 h at 110° C. The mixture was diluted with ethyl acetate (50 mL) and washed with brine (15 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to provide a crude product. Purification by preparative TLC (100% Ethyl Acetate) provided the title compound (80 mg, 76%). 1H NMR (400 MHz, CDCl3) δ: 1.65-1.70 (m, 1H); 1.72 (s, 3H), 1.78-1.84 (m, 1H), 1.95-2.05 (m, 1H), 2.40 (td, 1H), 3.35-3.41 (m, 1H), 3.52 (td, 1H), 3.87 (s, 3H), 4.11 (s, 3H), 5.83 (br. s., 1H), 6.49 (d, 1H), 7.10 (d, 1H), 7.41 (d, 1H), 7.64-7.67 (m, 2H), 7.77 (dd, 1H), 8.03 (s, 1H).

Workup

  1. washwashed with brine (15 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto provide a crude product
  6. customPurification by preparative TLC (100% Ethyl Acetate)

Sources & evidence

ORD record
ord-0562ccd762cf4d159fbb1b3c1ce53408
Source dataset
uspto-grants-2016_03
Patent number
US09278953B2

Reaction notes

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