(Diethylamino)sulfur trifluoride → 2-(2-Fluoro-4-((3-fluoroazetidin-1-yl)methyl)-phenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

HRID 1177542Notes

Reaction equation

HRID 1177542 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:26][N:27]2[CH2:30][CH:29](O)[CH2:28]2)[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:19][CH2:18]1)[N:11]=2.C(N(S(F)(F)[F:38])CC)C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH2:26][N:27]2[CH2:30][CH:29]([F:38])[CH2:28]2)[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:19][CH2:18]1)[N:11]=2

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 446014431-((3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)methyl)azetidin-3-ol

Product 1

HCID 445995252-(2-Fluoro-4-((3-fluoroazetidin-1-yl)methyl)-phenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a slurry of 1-((3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)methyl)azetidin-3-ol (0.100 g, 0.2 mmol) in 1 mL DCM under nitrogen at 0° C. was added (diethylamino)sulfur trifluoride (0.05 ml, 0.3 mmol). Upon consumption of starting material, the reaction was quenched with ice and 1 N NaOH. The reaction mixture was partitioned between water and DCM. The aqueous layer was extracted with DCM 3, and the combined cloudy organics were treated with a small amount of MeOH to give a solution, were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by RPHPLC, gradient, TFA/ACN in TFA/H2O provided material that was taken up in DCM and washed with saturated aq. NaHCO3, dried over sodium sulfate, filtered, and concentrated in vacuo to give 2-(2-fluoro-4-((3-fluoroazetidin-1-yl)methyl)-phenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine as a solid. MS (ESI) m/z: Calculated: 433.1; Observed: 434.1 (M++1).

Workup

  1. customUpon consumption of starting material
  2. customthe reaction was quenched with ice and 1 N NaOH
  3. customThe reaction mixture was partitioned between water and DCM
  4. extractionThe aqueous layer was extracted with DCM 3
  5. additionthe combined cloudy organics were treated with a small amount of MeOH
  6. customto give a solution
  7. dry with materialwere dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by RPHPLC, gradient, TFA/ACN in TFA/H2O provided material that
  11. washwashed with saturated aq. NaHCO3
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-371544ecf2ed4f21968bced068f52379
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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