Tetrahydrofuran → 2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(4-phenylhepta-1,6-dien-4-yl)thiazolo[5,4-b]pyridine

HRID 1177425Notes

Reaction equation

HRID 1177425 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[C:17]([CH:22]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:23][CH:24]=[CH2:25])[N:16]=3)=[C:9]([F:32])[CH:8]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1C[CH2:46][CH2:45][CH2:44]1.C(I)C=C>CN(C=O)C>[O:3]1[CH2:4][CH2:5][CH2:6][O:1][CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[C:17]([C:22]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)([CH2:46][CH:45]=[CH2:44])[CH2:23][CH:24]=[CH2:25])[N:16]=3)=[C:9]([F:32])[CH:8]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11166Allyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 686357552-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-phenylbut-3-enyl)-thiazolo[5,4-b]pyridine

Product 1

HCID 671121072-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(4-phenylhepta-1,6-dien-4-yl)thiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a slurry of 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-phenylbut-3-enyl)-thiazolo[5,4-b]pyridine (1.17 g, 2.62 mmol) in 20 mL DMF under argon was added sodium bis(trimethylsilyl)amide, 1.0M solution in tetrahydrofuran (3.28 mL, 3.28 mmol). The reaction mixture became deep blue/purple. After 2 min, allyl iodide (0.362 mL, 3.93 mmol) was added and the reaction became light orange after 1 min. After 5 min total, the reaction mixture was quenched with sat'd aq. NH4Cl, EtOAc, and water. The organic layer was washed with water, brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography, ISCO, 80 g, 0-40% EA/hexanes to give 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(4-phenylhepta-1,6-dien-4-yl)thiazolo[5,4-b]pyridine as a white foam. MS (ESI) m/z: Calculated: 486.2; Observed: 487.1 (M++1).

Workup

  1. waitthe reaction became light orange after 1 min
  2. waitAfter 5 min total
  3. customthe reaction mixture was quenched with sat'd aq. NH4Cl, EtOAc, and water
  4. washThe organic layer was washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography, ISCO, 80 g, 0-40% EA/hexanes

Sources & evidence

ORD record
ord-ffae73a642c44e17bf4212e1fe0366dd
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

Loading…