Sulfoxonium, trimethyl-, iodide (1:1) → 2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-(4-(benzyloxy)phenyl)cyclopropyl)thiazolo[5,4-b]pyridine

HRID 1177494Notes

Reaction equation

HRID 1177494 reaction equation
[CH3:1]C(C)([O-])C.[K+].[I-].C[S+](C)(C)=O.[O:13]1[CH2:18][CH2:17][CH2:16][O:15][CH:14]1[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[S:26][C:27]3[C:32]([N:33]=2)=[CH:31][CH:30]=[C:29]([C:34]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[CH:38][CH:37]=2)=[CH2:35])[N:28]=3)=[C:21]([F:50])[CH:20]=1>CS(C)=O.C1COCC1>[O:15]1[CH2:16][CH2:17][CH2:18][O:13][CH:14]1[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[S:26][C:27]3[C:32]([N:33]=2)=[CH:31][CH:30]=[C:29]([C:34]2([C:36]4[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]5[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=5)=[CH:38][CH:37]=4)[CH2:1][CH2:35]2)[N:28]=3)=[C:21]([F:50])[CH:20]=1

Participants

6

Reactant 3

HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 23665647Potassium tert-butoxideHCID 671114382-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-(4-(benzyloxy)phenyl)vinyl)thiazolo[5,4-b]pyridine

Product 1

HCID 671115132-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-(4-(benzyloxy)phenyl)cyclopropyl)thiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of potassium tert-butoxide (0.206 g, 1.83 mmol) and trimethylsulfoxonium iodide (0.404 g, 1.83 mmol) in 5 mL DMSO under nitrogen was added 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-(4-(benzyloxy)phenyl)vinyl)-thiazolo[5,4-b]pyridine (0.385 g, 0.734 mmol) as a solution in 6 mL THF (min volume to dissolve) slowly dropwise via addition funnel over 1 h. The cloudy reaction mixture was allowed to stir for 4 h and was quenched with ice. The reaction mixture was partitioned between water and EtOAc. The organic layer was washed with water, brine, dried, and concentrated in vacuo to give an oil/solid which was purified by silica gel chromatography 0-100% EA/hexanes to give 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-(4-(benzyloxy)phenyl)cyclopropyl)thiazolo[5,4-b]pyridine as a yellow solid. The aqueous suspension from the extraction was further extracted with DCM, the combined org extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to give additional 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-(4-(benzyloxy)phenyl)-cyclopropyl)thiazolo[5,4-b]pyridine. MS (ESI) m/z: calculated: 538.2; Observed: 539.1 (M++1).

Workup

  1. additionslowly dropwise via addition funnel over 1 h
  2. customThe cloudy reaction mixture
  3. customwas quenched with ice
  4. customThe reaction mixture was partitioned between water and EtOAc
  5. washThe organic layer was washed with water, brine
  6. customdried
  7. concentrationconcentrated in vacuo
  8. customto give an oil/solid which
  9. customwas purified by silica gel chromatography 0-100% EA/hexanes

Sources & evidence

ORD record
ord-cfc0f9bd239b4bf4b14e3f9e9bec5652
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

Loading…