Sulfoxonium, trimethyl-, iodide (1:1) → Methyl 1-((3-fluoro-4-(5-(1-(4-fluorophenyl)-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylate

HRID 1177500Notes

Reaction equation

HRID 1177500 reaction equation
[CH3:1]C(C)([O-])C.[K+].[I-].C[S+](C)(C)=O.[F:13][C:14]1[CH:15]=[C:16]([CH2:38][N:39]2[CH2:42][CH:41]([C:43]([O:45][CH3:46])=[O:44])[CH2:40]2)[CH:17]=[CH:18][C:19]=1[C:20]1[S:21][C:22]2[C:27]([N:28]=1)=[CH:26][CH:25]=[C:24]([C:29]([C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1)=[CH2:30])[N:23]=2>CS(C)=O.C1COCC1>[F:13][C:14]1[CH:15]=[C:16]([CH2:38][N:39]2[CH2:40][CH:41]([C:43]([O:45][CH3:46])=[O:44])[CH2:42]2)[CH:17]=[CH:18][C:19]=1[C:20]1[S:21][C:22]2[C:27]([N:28]=1)=[CH:26][CH:25]=[C:24]([C:29]1([C:31]3[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=3)[CH2:1][CH2:30]1)[N:23]=2

Participants

6

Reactant 3

HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 23665647Potassium tert-butoxideHCID 67111924Methyl 1-((3-fluoro-4-(5-(1-(4-fluorophenyl)vinyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylate

Product 1

HCID 67111665Methyl 1-((3-fluoro-4-(5-(1-(4-fluorophenyl)-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of potassium tert-butoxide (0.080 g, 0.71 mmol) and trimethylsulfoxonium iodide (0.16 g, 0.71 mmol) in 2 mL DMSO was added slowly dropwise a solution of methyl 1-((3-fluoro-4-(5-(1-(4-fluorophenyl)vinyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylate (0.170 g, 0.36 mmol) in 2 mL THF, with 1 mL rinse. The solution became colored. After 30 min, the reaction mixture was quenched with sat'd aq. NH4Cl and EtOAc. The organic layer was washed with water, then brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The material was treated with DCM and adsorbed onto 1.5 g silica gel and passed through a Redi-Sep® pre-packed silica gel column (12 g) using 0-100% EtOAc/hexane. The product-containing fractions were concentrated to afford methyl 1-((3-fluoro-4-(5-(1-(4-fluorophenyl)-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylate as a yellow solid. MS (ESI) m/z: calculated: 491.2; Observed: 492.1 (M++1).

Workup

  1. washwith 1 mL rinse
  2. customthe reaction mixture was quenched with sat'd aq. NH4Cl and EtOAc
  3. washThe organic layer was washed with water
  4. dry with materialbrine, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionThe material was treated with DCM
  8. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-35206c728b6c4ced8d8cf8ba5b59adc5
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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