Cesium fluoride → 2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-(4-(benzyloxy)phenyl)vinyl)thiazolo[5,4-b]pyridine

HRID 1177493Notes

Reaction equation

HRID 1177493 reaction equation
[F-].[Cs+].[O:3]1[CH2:8][CH2:7][CH2:6][O:5][CH:4]1[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][C:17]3[C:22]([N:23]=2)=[CH:21][CH:20]=[C:19](Cl)[N:18]=3)=[C:11]([F:25])[CH:10]=1.[CH2:26]([O:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]([Sn](CCCC)(CCCC)CCCC)=[CH2:41])=[CH:36][CH:35]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C=O)C.CC(=O)OCC.[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>[O:3]1[CH2:8][CH2:7][CH2:6][O:5][CH:4]1[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][C:17]3[C:22]([N:23]=2)=[CH:21][CH:20]=[C:19]([C:40]([C:37]2[CH:38]=[CH:39][C:34]([O:33][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:35][CH:36]=2)=[CH2:41])[N:18]=3)=[C:11]([F:25])[CH:10]=1

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 18436367{1-[4-(Benzyloxy)phenyl]ethenyl}(tributyl)stannaneHCID 591748622-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-chlorothiazolo[5,4-b]pyridine

Product 1

HCID 671114382-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-(4-(benzyloxy)phenyl)vinyl)thiazolo[5,4-b]pyridine

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
55 °C

Procedure

A slurry of cesium fluoride (0.325 g, 2.14 mmol), CuI 0.0271 g, 0.143 mmol), tetrakis(triphenylphosphine) palladium (0) (0.0824 g, 0.0713 mmol), 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-chlorothiazolo[5,4-b]pyridine (0.500 g, 1.43 mmol), and crude (1-(4-(benzyloxy)-phenyl)vinyl)tributylstannane (1.07 g, 2.14 mmol) in 5 mL DMF was flushed with argon, sealed, and heated to 55° C. overnight. The reaction mixture was diluted with EA, filtered through celite, rinsing with EA. The filtrate was washed with water, brine, dried over sodium sulfate, filtered, and concentrated. The residue was adsorbed onto 4 g silica gel from DCM, concentrated, and purified by ISCO 40 g, 0-100% EA/hexanes to give 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-(4-(benzyloxy)phenyl)vinyl)thiazolo[5,4-b]pyridine as an orange solid. MS (ESI) m/z: calculated: 524.2; Observed: 525.1 (M++1).

Workup

  1. customsealed
  2. filtrationfiltered through celite
  3. washrinsing with EA
  4. washThe filtrate was washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. concentrationconcentrated
  9. custompurified by ISCO 40 g, 0-100% EA/hexanes

Sources & evidence

ORD record
ord-ab63040e05d24648a271a578f48bba7e
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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