7-Chlorothieno[3,2-b]pyridine → 2-(5-(1,3-Dioxolan-2-yl)pyridin-2-yl)-7-chlorothieno[3,2-b]pyridine

HRID 1400913Notes

Reaction equation

HRID 1400913 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.Br[C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[O:27][CH2:26][CH2:25][O:24]2)=[CH:19][N:18]=1>C1COCC1.[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:24]1[CH2:25][CH2:26][O:27][CH:23]1[C:20]1[CH:21]=[CH:22][C:17]([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:18][CH:19]=1

Participants

7

Reactant 3

HCID 112752517-Chlorothieno[3,2-b]pyridineHCID 184696682-Bromo-5-(1,3-dioxolan-2-YL)pyridineHCID 178418339Butyllithium

Product 1

HCID 579195542-(5-(1,3-Dioxolan-2-yl)pyridin-2-yl)-7-chlorothieno[3,2-b]pyridineYield 98%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 7-chlorothieno[3,2-b]pyridine (14 g, 82.4 mmol) in THF (137 mL) was added, at −78° C., a solution of n-BuLi (34.4 mL, 89.3 mmol, 2.6 M in hexanes) and the reaction mixture was stirred for 10 min. A solution of ZnCl2 (89 mL, 89.3 mmol, 1.0 M in Et2O) was added and the mixture was stirred at RT for 10 min. Pd(PPh3)4 (3.18 g, 2.75 mmol) was added along with a solution of 300 (15.8 g, 68.7 mmol) in THF (50 mL) and the reaction mixture was heated to reflux under an atmosphere of N2 gas for 1 hour. The reaction mixture was then cooled to RT, and partitioned between saturated ammonium hydroxide solution and EtOAc. The organic phase was collected, dried over anhydrous Na2SO4, filtered and concentrated. The resultant material was triturated with EtOAc to afford the title compound 301 (21.4 g, 98% yield) as a beige solid. 1H NMR (300 MHz, DMSO-d6) δ (ppm): 8.71 (d, J=2.1 Hz, 1H), 8.67 (d, J=5.1 Hz, 1H), 8.49 (s, 1H), 8.36 (d, J=8.1 Hz, 1H), 8.01 (dd, J=8.1, 2.1 Hz, 1H), 7.61 (d, J=5.1 Hz, 1H), 5.91 (s, 1H), 4.16-3.96 (m, 4H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux under an atmosphere of N2 gas for 1 hour
  3. temperatureThe reaction mixture was then cooled to RT
  4. custompartitioned between saturated ammonium hydroxide solution and EtOAc
  5. customThe organic phase was collected
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resultant material was triturated with EtOAc

Sources & evidence

ORD record
ord-7ad4e22a26ee452a9f016015d493b5b8
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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