Sodium Carbonate → HCID 11198099, compound

HRID 900195Notes

Reaction equation

HRID 900195 reaction equation
Br[C:2]1[CH:18]=[CH:17][C:5]2[N:6]=[C:7]([CH2:9][CH2:10][N:11]3[CH2:15][CH2:14][CH2:13][C@H:12]3[CH3:16])[S:8][C:4]=2[CH:3]=1.[N:19]1[CH:24]=[CH:23][CH:22]=[C:21](B(O)O)[CH:20]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>CC(O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:16][C@@H:12]1[CH2:13][CH2:14][CH2:15][N:11]1[CH2:10][CH2:9][C:7]1[S:8][C:4]2[CH:3]=[C:2]([C:21]3[CH:20]=[N:19][CH:24]=[CH:23][CH:22]=3)[CH:18]=[CH:17][C:5]=2[N:6]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27343783-Pyridinylboronic acidHCID 21041499HCID 21041499, compound

Product 1

HCID 11198099HCID 11198099, compoundYield 68.7%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 6-bromo-2-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-benzothiazole (0.3 g, 0.9 mmol), 3-pyridinyl boronic acid (0.17 g, 1.4 mmol) and 2-(dicyclohexylphosphino)biphenyl (65 mg, 0.2 mmol) in 15 mL of IPA was purged wth nitrogen. Dichlorobis(triphenylphosphine)palladium 11 (65 mg, 0.1 mmol) was added. Sodium carbonate (0.15 g, 1.35 mmol) was dissolved in 5 g of water, purged with nitrogen, and added to the above mixture. The mixture was heated to 65° C. under nitrogen for 16 hr. After cooling to room temperature 20 mL of methylene chloride was added and the solid was filtered off. The filtrate was concentrated to oil and dissolved in 10 mL of 2N HCl. The acidic aqueous layer was washed with 10 mL methylene chloride, the pH adjusted with 4N NaOH to pH 10, and the product free base was extracted with 20 mL methylene chloride. The methylene chloride layer was concentrated to dryness and purified by column chromatography (silica gel, 10:90 MeOH:CHCl3) to give the pure 2-[2-(2-Methyl-pyrrolidin-1-yl)-ethyl]-6-pyridin-3-yl-benzothiazole (0.2 g, 67% yield). 1H NMR (CDCl3, 400 MHz) δ 1.14 (d, 3H, J=8 Hz), 1.42-1.51 (m, 1H), 1.71-1.86 (m, 2H), 1.92-2.00 (m, 1H), 2.27 (q, 1H, J=8 Hz), 2.41-2.48 (m, 1H), 2.60-2.67 (m, 1H), 3.22-3.37 (m, 4H), 7.36-7.39 (m, 1H), 7.64 (broad d, 1H, J=8 Hz), 7.90 (broad d, 1H, J=8 Hz), 8.03-8.05 (m, 2H), 8.60 (d, 1H, J=4 Hz), 8.89 (d, 1H, J=1.5 Hz); 13C NMR (CDCl3, 400 MHz) δ 19.3, 22.2, 33.0, 34.0, 52.7, 53.8, 59.9, 119.7, 122.6, 123.3, 125.0, 134.2, 135.9, 136.2, 148.0, 148.1, 152.3, 170.7; (DCl/NH3) m/z 324 (M+H)+.

Workup

  1. customwas purged wth nitrogen
  2. custompurged with nitrogen
  3. additionadded to the above mixture
  4. temperatureAfter cooling to room temperature 20 mL of methylene chloride
  5. additionwas added
  6. filtrationthe solid was filtered off
  7. concentrationThe filtrate was concentrated to oil
  8. dissolutiondissolved in 10 mL of 2N HCl
  9. washThe acidic aqueous layer was washed with 10 mL methylene chloride
  10. extractionthe product free base was extracted with 20 mL methylene chloride
  11. concentrationThe methylene chloride layer was concentrated to dryness
  12. custompurified by column chromatography (silica gel, 10:90 MeOH:CHCl3)

Sources & evidence

ORD record
ord-502dbe26eedf46968518bb0981afb27d
Source dataset
uspto-grants-2008_04
Patent number
US07358263B2

Reaction notes

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