Tetrahydrofuran → 1-[6-(2-Ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-ylmethyl)naphthalen-2-yl]cyclopent-3-ene carboxylic acid ethyl ester

HRID 481407Notes

Reaction equation

HRID 481407 reaction equation
[CH2:1]([O:3][C:4](=[O:30])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH2:16][N:17]3[C:21]4=[N:22][C:23]([CH3:27])=[CH:24][C:25]([CH3:26])=[C:20]4[N:19]=[C:18]3[CH2:28][CH3:29])[CH:12]=2)[CH:7]=1)[CH3:2].CC(C)([O-])C.[K+].[CH2:37]1[CH2:41]O[CH2:39][CH2:38]1.ClC/C=C\CCl>C1COCC1.CN1C(=O)N(C)CCC1>[CH2:1]([O:3][C:4]([C:5]1([C:6]2[CH:15]=[CH:14][C:13]3[C:8](=[CH:9][CH:10]=[C:11]([CH2:16][N:17]4[C:21]5=[N:22][C:23]([CH3:27])=[CH:24][C:25]([CH3:26])=[C:20]5[N:19]=[C:18]4[CH2:28][CH3:29])[CH:12]=3)[CH:7]=2)[CH2:39][CH:38]=[CH:37][CH2:41]1)=[O:30])[CH3:2]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 64321151,4-Dichloro-cis-2-buteneHCID 23665647Potassium tert-butoxide2×HCID 67667088[6-(2-Ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-ylmethyl)naphthalen-2-yl]acetic acid ethyl ester2×

Product 1

HCID 676668611-[6-(2-Ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-ylmethyl)naphthalen-2-yl]cyclopent-3-ene carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 22565281tetrahydrofuran 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinoneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of the product of Step 3, above (52) (95 mg, 0.24 mmol), in THF/DMPU (1 ml/0.25 ml) at -78° C., was added 1.0M solution of potassium t-butoxide in THF (0.24 ml, 0.24 mmol). The solution was stirred for 15 minutes at -78° C. and cis-1,4-dichlorobut-2-ene (0.025 ml, 0.24 mmol) was added. The reaction mixture was stirred at -78° C. for 10 minutes and a second equivalent of 1.0M potassium t-butoxide solution was added. The reaction mixture was warmed to -50° C. for 15 minutes, the cooling bath was removed and the mixture was stirred at ambient temperature for 15 minutes. The reaction was then heated to 80° C. for 2 hours. The reaction was cooled to ambient temperature, quenched with concentrated acetic acid, diluted with EtOAc and extracted from brine. The combined organics were then dried over MgSO4, filtered and concentrated to dryness. The crude material was then chromatographed on silica gel using 50% EtOAc in hexanes as the eluant to yield the title compound (53) (35 mg).

Workup

  1. stirringThe reaction mixture was stirred at -78° C. for 10 minutes
  2. temperatureThe reaction mixture was warmed to -50° C. for 15 minutes
  3. customthe cooling bath was removed
  4. stirringthe mixture was stirred at ambient temperature for 15 minutes
  5. temperatureThe reaction was then heated to 80° C. for 2 hours
  6. temperatureThe reaction was cooled to ambient temperature
  7. customquenched with concentrated acetic acid
  8. additiondiluted with EtOAc
  9. extractionextracted from brine
  10. dry with materialThe combined organics were then dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated to dryness
  13. customThe crude material was then chromatographed on silica gel using 50% EtOAc in hexanes as the eluant

Sources & evidence

ORD record
ord-8224d7b2024047db92ca965fce22899a
Source dataset
uspto-grants-1998_08
Patent number
US05789415

Reaction notes

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