Tetrabutylammonium Fluoride → 3-[(1R)-1-(2-chlorophenyl)-2-hydroxyethoxy]-5-[6-(hydroxymethyl)-1H-imidazo[4,5-c]pyridin-1-yl]thiophene-2-carboxamide

HRID 2391655Notes

Reaction equation

HRID 2391655 reaction equation
[Si]([O:8][CH2:9][C@@H:10]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[Cl:44])[O:11][C:12]1[CH:16]=[C:15]([N:17]2[C:25]3[CH:24]=[C:23]([CH2:26][O:27][Si](C(C)(C)C)(C)C)[N:22]=[CH:21][C:20]=3[N:19]=[CH:18]2)[S:14][C:13]=1[C:35]([NH2:37])=[O:36])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[Cl:44][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=1[C@@H:10]([O:11][C:12]1[CH:16]=[C:15]([N:17]2[C:25]3[CH:24]=[C:23]([CH2:26][OH:27])[N:22]=[CH:21][C:20]=3[N:19]=[CH:18]2)[S:14][C:13]=1[C:35]([NH2:37])=[O:36])[CH2:9][OH:8]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 687661183-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-(2-chlorophenyl)ethoxy]-5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]thiophene-2-carboxamide

Product 1

HCID 687663103-[(1R)-1-(2-chlorophenyl)-2-hydroxyethoxy]-5-[6-(hydroxymethyl)-1H-imidazo[4,5-c]pyridin-1-yl]thiophene-2-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 236 mg of 3-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-(2-chlorophenyl)ethoxy]-5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]thiophene-2-carboxamide in 15 ml THF is cooled to 0° C. At 0° C. 0.26 ml tetra-n-butylammonium fluoride (˜75% in H20) are added. The reaction mixture is allowed to warm to room temperature and stirred for one hour. The solvent is evaporated under reduced pressure and the residue is treated with 15 ml dichloromethane and 10 ml saturated aqueous NaHCO3 solution. The phases are separated; the aqueous phase is extracted with 10 ml dichloromethane. The combined organic phase is dried over Na2SO4, filtered and concentrated to dryness. The raw product is purified by flash chromatography over silica gel Flash NH2 [eluent: dichloromethane/methanol, with a gradient of 100/0 to 90/10 (v/v)]. The title product is obtained after a second purification in preparative HPLC (ammonium formate buffer/acetonitrile, elution gradient 80/20 to 30/70 (v/v)).

Workup

  1. customAt 0° C
  2. temperatureto warm to room temperature
  3. customThe solvent is evaporated under reduced pressure
  4. additionthe residue is treated with 15 ml dichloromethane and 10 ml saturated aqueous NaHCO3 solution
  5. customThe phases are separated
  6. extractionthe aqueous phase is extracted with 10 ml dichloromethane
  7. dry with materialThe combined organic phase is dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe raw product is purified by flash chromatography over silica gel Flash NH2 [eluent

Sources & evidence

ORD record
ord-e148a9d0cd0f48d98974fb3f6b3abacb
Source dataset
uspto-grants-2012_09
Patent number
US08273890B2

Reaction notes

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