Sodium Carbonate → 1-Methyl-2-[5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridin-3-yl]-1H-indole

HRID 2305102Notes

Reaction equation

HRID 2305102 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1B(O)O.Br[C:15]1[CH:16]=[C:17]([O:21][CH2:22][C@@H:23]2[CH2:27][CH2:26][CH2:25][N:24]2[CH3:28])[CH:18]=[N:19][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:15]1[CH:16]=[C:17]([O:21][CH2:22][C@@H:23]2[CH2:27][CH2:26][CH2:25][N:24]2[CH3:28])[CH:18]=[N:19][CH:20]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridineHCID 22733820(1-Methyl-1H-indol-2-yl)boronic acid

Product 1

HCID 443723681-Methyl-2-[5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridin-3-yl]-1H-indole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of the compound from step 36a and 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)-pyridine (270 mg, 1.0 mmol) in toluene (5.0 mL) was added Pd(0) (25 mg) and Na2CO3 (1 mL of a 2 M solution), and the mixture was heated at reflux for 60 hours. The solvent was removed under vacuum, and the residue was purified by chromatography on silica gel to afford 105 mg of the title compound. MS (CI/NH3) m/z 322 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.80 (m, 3H), 2.05 (m, 1H), 2.32 (m, 1H), 2.50 (s, 3H), 2.70 (m, 1H), 3.13 (m, 1H), 3.78 (s, 3H), 4.04 (m, 2H), 6.62 (s, 1H), 7.18 (m, 2H), 7.35 (m, 2H), 7.66 (m, 1H), 8.38 (m, 2H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 60 hours
  3. customThe solvent was removed under vacuum
  4. customthe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-e63bf781e41e49b5a62eac11436a0a06
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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