Potassium Carbonate → 4-{2-[2-(2-Methyl-pyrrolidin-1-yl)-ethyl]-benzothiazol-5-yl}-benzonitrile

HRID 900187

Reaction equation

HRID 900187 reaction equation
C([O-])([O-])=O.[K+].[K+].[F-].[Cs+].[C:9]([C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1)#[N:10].Br[C:21]1[CH:22]=[CH:23][C:24]2[S:28][C:27]([CH2:29][CH2:30][N:31]3[CH2:35][CH2:34][CH2:33][CH:32]3[CH3:36])=[N:26][C:25]=2[CH:37]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:36][CH:32]1[CH2:33][CH2:34][CH2:35][N:31]1[CH2:30][CH2:29][C:27]1[S:28][C:24]2[CH:23]=[CH:22][C:21]([C:14]3[CH:15]=[CH:16][C:11]([C:9]#[N:10])=[CH:12][CH:13]=3)=[CH:37][C:25]=2[N:26]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 25953Cesium fluorideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27343264-Cyanophenylboronic acidHCID 219800005-Bromo-2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]benzothiazole

Product 1

HCID 219800314-{2-[2-(2-Methyl-pyrrolidin-1-yl)-ethyl]-benzothiazol-5-yl}-benzonitrileYield 31.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a reaction flask containing K2CO3 (0.326 g, 1.5 mmol), CsF (0.233 g, 1.5 mmol), and (0.19 g, 1.3 mmol) of 4-cyanophenyl boronic acid was added a solution of 5-bromo-2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-benzothiazole (0.25 g, 0.77 mmol) in 3 mL of toluene. The resulting mixture was purged with nitrogen, and then 2-dicyclohexylphosphinobiphenyl (54 mg, 0.15 mmol) and Pd2(dba)3 (70 mg, 0.08 mmol) were added. The resulting reaction mixture was then heated at 90° C. for 2 hr. At completion, the reaction was washed with water, then diluted with with CH2Cl2, and purified by column chromatography (silica gel, 10% MeOH/CH2Cl2), to give 4-{2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-benzothiazol-5-yl}-benzonitrile in an isolated yield of 31.5%. The hydrochloride salt of the product was formed by adding 6N HCl (2 equivalents) in isopropanol solution and then diluting with 1 mL of isopropanol, followed by removal of solvent. 1H NMR (400 MHz, Methanol d4) δ 1.47 (d, J=6.45 Hz, 3 H) 1.72 (dd, J=12.76, 8.37 Hz, 1 H) 2.29 (m, 2 H) 3.23 (m, 3 H) 3.36 (t, J=7.14 Hz, 1 H) 3.62 (m, 3 H) 3.99 (m, 1 H) 7.68 (dd, J=8.44, 1.72 Hz, 1 H) 7.77 (m, 4 H) 8.01 (d, J=8.37 Hz, 1 H) 8.17 (d, J=1.51 Hz, 1 H) [M+H]+ at m/z 348.

Workup

  1. customThe resulting mixture was purged with nitrogen
  2. customThe resulting reaction mixture
  3. washAt completion, the reaction was washed with water
  4. additiondiluted with with CH2Cl2
  5. custompurified by column chromatography (silica gel, 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-16944326f26b4b2db640a8dd18536342
Source dataset
uspto-grants-2008_04
Patent number
US07358263B2

Linked notes

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