Hydrochloric Acid → 2-(2-Fluoro-4-vinylphenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

HRID 1177410Notes

Reaction equation

HRID 1177410 reaction equation
C[Si](C[Mg]Cl)(C)C.[F:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=1[C:17]1[S:18][C:19]2[C:24]([N:25]=1)=[CH:23][CH:22]=[C:21]([C:26]1([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:28][CH2:27]1)[N:20]=2)[CH:12]=O.[CH3:35]C(C)([O-])C.[K+].Cl>C1COCC1>[F:8][C:9]1[CH:10]=[C:11]([CH:12]=[CH2:35])[CH:14]=[CH:15][C:16]=1[C:17]1[S:18][C:19]2[C:24]([N:25]=1)=[CH:23][CH:22]=[C:21]([C:26]1([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:27][CH2:28]1)[N:20]=2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 591749073-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzaldehydeHCID 178418680HCID 178418680, compound

Product 1

HCID 591749092-(2-Fluoro-4-vinylphenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Trimethylsilylmethylmagnesium chloride, 1.1 M solution in THF (15 mL) was added dropwise to a solution at 0° C. of 3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)benzaldehyde (4.00 g, 11 mmol) in THF (80 mL) and the reaction mixture was stirred for 30 min at 0° C. The reaction mixture was quenched with 1 N aq. HCl and extracted with EtOAc twice, dried over MgSO4 and concentrated in vacuo. The residue was dissolved in THF (100 mL), and cooled to 0° C. in ice bath. The slurry of potassium t-butoxide (2.4 g, 21 mmol) in THF (12 mL) was added slowly. At the end of the addition the reaction mixture was allowed to stir for 30 min at 0° C. At this time 1 N HCl was added and the mixture was extracted with EtOAc and the organic layer was dried over MgSO4. The residue was concentrated in vacuo and purified by silica gel chromatography to afford 2-(2-fluoro-4-vinylphenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine. MS (ESI) m/z: calculated: 372.1; Observed: 373.0 (M++1).

Workup

  1. customThe reaction mixture was quenched with 1 N aq. HCl
  2. extractionextracted with EtOAc twice
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in THF (100 mL)
  6. temperaturecooled to 0° C. in ice bath
  7. additionAt the end of the addition the reaction mixture
  8. stirringto stir for 30 min at 0° C
  9. extractionthe mixture was extracted with EtOAc
  10. dry with materialthe organic layer was dried over MgSO4
  11. concentrationThe residue was concentrated in vacuo
  12. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-c4e11e6209cb4888b65773024a7562f7
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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