Imidazole → 4-(1-Ethylpiperazin-4-yl)-6-[3-(2-hydroxyethoxy)phenyl]thieno[3,2-c]pyridine dihydrochloride

HRID 1251181Notes

Reaction equation

HRID 1251181 reaction equation
N[C:2]1[N:7]=[C:6](Br)[C:5]2[CH:9]=[CH:10][S:11][C:4]=2[CH:3]=1.Br[C:13]1[C:18]2C=CSC=2[CH:16]=[C:15](Br)[N:14]=1.Br[C:24]1[C:29]2C=CSC=2C(Br)=C(Br)N=1.C([O:38][CH2:39][CH2:40][O:41][C:42]1[CH:47]=[CH:46][CH:45]=[C:44]([Sn](CCCC)(CCCC)CCCC)[CH:43]=1)(=O)C.[Si]([Cl:68])(C(C)(C)C)(C)C.[NH:69]1C=CN=C1>CN(C)C=O>[ClH:68].[ClH:68].[CH2:24]([N:14]1[CH2:13][CH2:18][N:69]([C:6]2[C:5]3[CH:9]=[CH:10][S:11][C:4]=3[CH:3]=[C:2]([C:46]3[CH:45]=[CH:44][CH:43]=[C:42]([O:41][CH2:40][CH2:39][OH:38])[CH:47]=3)[N:7]=2)[CH2:16][CH2:15]1)[CH3:29]

Participants

8

Reactant 6

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 225027784,6,7-Tribromothieno[3,2-c]pyridineHCID 225030284,6-Dibromothieno[3,2-c]pyridineHCID 225034234-Bromothieno[3,2-C]pyridin-6-amineHCID 691836713-Tributylstannylphenoxyethyl acetate

Product 1

HCID 225033624-(1-Ethylpiperazin-4-yl)-6-[3-(2-hydroxyethoxy)phenyl]thieno[3,2-c]pyridine dihydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-Amino-4-bromothieno[3,2-c]pyridine (894 mg) was treated in the same manner as in Example 245-1, to obtain a mixture of 4,6-dibromothieno[3,2-c]pyridine and 4,6,7-tribromothieno[3,2-c]pyridine (6:4). Continuously, the mixture was treated in the same manner as in Example 245-2 and then treated with 3-tributylstannylphenoxyethyl acetate (394 mg) in the same manner as in Example 300-4. Then, the reaction mixture was dissolved in N,N-dimethylformamide (15 ml), followed by the addition of t-butyldimethylsilyl chloride (241 mg) and imidazole (136 mg), and the mixture was stirred for 1 hr at room temperature. The reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with water, dried (over MgSO4) and evaporated. The residue was dissolved in tetrahydrofuran (12 ml), followed by the addition of 2.5M n-butyl lithium/hexane solution (480 ml) in nitrogen atmosphere at −70° C., and the mixture was stirred for 30 min. Then, an aqueous solution of saturated ammonium chloride was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried (over MgSO4) and evaporated. The residue was purified by (NH) silica gel column chromatography (ethyl acetate/hexane system). The resulting product was then converted into a hydrochloride in a conventional manner, to give the hydrochloride of the title compound as a colorless amorphous (288 mg, yield; 15%).

Workup

  1. customto obtain
  2. additionContinuously, the mixture was treated in the same manner as in Example 245-2
  3. customThe reaction solution was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with water
  5. dry with materialdried (over MgSO4)
  6. customevaporated
  7. dissolutionThe residue was dissolved in tetrahydrofuran (12 ml)
  8. additionfollowed by the addition of 2.5M n-butyl lithium/hexane solution (480 ml) in nitrogen atmosphere at −70° C.
  9. stirringthe mixture was stirred for 30 min
  10. additionThen, an aqueous solution of saturated ammonium chloride was added
  11. extractionthe mixture was extracted with ethyl acetate
  12. washThe organic layer was washed with water
  13. dry with materialdried (over MgSO4)
  14. customevaporated
  15. customThe residue was purified by (NH) silica gel column chromatography (ethyl acetate/hexane system)

Sources & evidence

ORD record
ord-7e7ed91b3cd543fba1634b9bde0b6869
Source dataset
uspto-grants-2002_01
Patent number
US06340759B1

Reaction notes

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