7-Chlorothieno[3,2-b]pyridine → 2-(5-(1,3-Dioxan-2-yl)-1-methyl-1H-imidazol-2-yl)-7-chlorothieno[3,2-b]pyridine

HRID 1026789Notes

Reaction equation

HRID 1026789 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12.[Li]CCCC.[O:16]1[CH2:21][CH2:20][CH2:19][O:18][CH:17]1[C:22]1[N:26]([CH3:27])[C:25](I)=[N:24][CH:23]=1>C1COCC1.[OH-].[NH4+].CCOC(C)=O.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:18]1[CH2:19][CH2:20][CH2:21][O:16][CH:17]1[C:22]1[N:26]([CH3:27])[C:25]([C:9]2[S:10][C:3]3[C:4](=[N:5][CH:6]=[CH:7][C:2]=3[Cl:1])[CH:8]=2)=[N:24][CH:23]=1

Participants

9

Reactant 3

HCID 112752517-Chlorothieno[3,2-b]pyridineHCID 579195385-(1,3-Dioxan-2-yl)-2-iodo-1-methyl-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 579194992-(5-(1,3-Dioxan-2-yl)-1-methyl-1H-imidazol-2-yl)-7-chlorothieno[3,2-b]pyridineYield 87.1%

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Procedure

To a solution of 7-chlorothieno[3,2-b]pyridine (1) [Klemm, L. H.; Louris, J. N.; Boisvert, W.; Higgins, C.; Muchiri, D. R.; J. Heterocyclic Chem., 22, 1985, 1249-1252] (11.7 g, 69.0 mmol) in THF (300 mL) was added, at −78° C., a solution of n-BuLi (30.46 mL, 76 mmol, 2.5 M in hexanes) and the reaction mixture was stirred for 10 min. A solution of ZnCl2 (76.15 mL, 76 mmol, 1.0 M in Et2O) was added and the mixture was stirred at RT for 10 min. Pd(PPh3)4 (2.287 mg, 0.104 mmol) was added along with a solution of 39 (5.82 g, 19.79 mmol) in THF (20 mL) and the reaction mixture was heated to reflux under an atmosphere of N2 gas for 4 hours. The reaction was then cooled to RT, and diluted with ammonium hydroxide and EtOAc. The organic phase was collected, dried over Na2SO4, filtered and concentrated. The resultant material was triturated with Et2O to afford the title compound 40 (5.79 g, 87% yield) as a white solid. MS (m/z): 336.1 (M+H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux under an atmosphere of N2 gas for 4 hours
  3. temperatureThe reaction was then cooled to RT
  4. customThe organic phase was collected
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resultant material was triturated with Et2O

Sources & evidence

ORD record
ord-d78fef47953f4e4187e86618eb6e48c8
Source dataset
uspto-grants-2014_05
Patent number
US08729268B2

Reaction notes

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