Cesium fluoride → Methyl 1-((3-fluoro-4-(5-(1-(4-fluorophenyl)vinyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylate

HRID 1177499Notes

Reaction equation

HRID 1177499 reaction equation
[F-].[Cs+].Cl[C:4]1[N:9]=[C:8]2[S:10][C:11]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][N:20]4[CH2:23][CH:22]([C:24]([O:26][CH3:27])=[O:25])[CH2:21]4)=[CH:15][C:14]=3[F:28])=[N:12][C:7]2=[CH:6][CH:5]=1.C([Sn](CCCC)(CCCC)[C:34]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)=[CH2:35])CCC>CN(C=O)C.CCOC(C)=O.[Cu]I.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:28][C:14]1[CH:15]=[C:16]([CH2:19][N:20]2[CH2:23][CH:22]([C:24]([O:26][CH3:27])=[O:25])[CH2:21]2)[CH:17]=[CH:18][C:13]=1[C:11]1[S:10][C:8]2[C:7]([N:12]=1)=[CH:6][CH:5]=[C:4]([C:34]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)=[CH2:35])[N:9]=2

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 67111781Tributyl(1-(4-fluorophenyl)vinyl)stannaneHCID 86638707Methyl 1-((4-(5-chlorothiazolo[5,4-b]pyridine-2-yl)-3-fluorophenyl)methyl)azetidine-3-carboxylate

Product 1

HCID 67111924Methyl 1-((3-fluoro-4-(5-(1-(4-fluorophenyl)vinyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

A slurry of cesium fluoride (0.310 g, 2.04 mmol), copper(I) iodide (0.0194 g, 0.102 mmol), tetrakis(triphenylphosphine) palladium (0) (0.0590 g, 0.0510 mmol), methyl 1-((4-(5-chlorothiazolo[5,4-b]pyridine-2-yl)-3-fluorophenyl)methyl)azetidine-3-carboxylate (0.400 g, 1.02 mmol), tributyl(1-(4-fluorophenyl)-vinyl)stannane (0.504 g, 1.22 mmol) in 2 mL DMF was sealed and heated to 45° C. overnight. The reaction mixture became purple/black and was allowed to stir at ambient temperature for 24 h. The reaction mixture was diluted with EtOAc and filtered through celite, then the filtrate was washed with water. The water layer was removed, and the EA layer was treated with DCM until only slightly cloudy, the organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting material was purified by silica gel chromatography, 0-100% EA/hexanes to give methyl 1-((3-fluoro-4-(5-(1-(4-fluorophenyl)vinyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylate as an orange solid. MS (ESI) m/z: calculated: 477.1; Observed: 478.1 (M++1).

Workup

  1. filtrationfiltered through celite
  2. washthe filtrate was washed with water
  3. customThe water layer was removed
  4. additionthe EA layer was treated with DCM until only slightly cloudy
  5. dry with materialthe organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting material was purified by silica gel chromatography, 0-100% EA/hexanes

Sources & evidence

ORD record
ord-4b550b3540214eb38ef70e8d35dee4e0
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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