Tetrahydrofuran → 2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(4-phenylocta-1,7-dien-4-yl)thiazolo[5,4-b]pyridine

HRID 1177431Notes

Reaction equation

HRID 1177431 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:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:24][CH:25]=[CH2:26])[N:16]=3)=[C:9]([F:33])[CH:8]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1C[CH2:47][CH2:46][CH2:45]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:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)([CH2:23][CH2:24][CH:25]=[CH2:26])[CH2:47][CH:46]=[CH2:45])[N:16]=3)=[C:9]([F:33])[CH:8]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11166Allyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 686359872-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-phenylpent-4-enyl)thiazolo[5,4-b]pyridine

Product 1

HCID 671119362-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(4-phenylocta-1,7-dien-4-yl)thiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Argon was bubbled through a slurry of 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-phenylpent-4-enyl)thiazolo[5,4-b]pyridine (1.02 g, 2.21 mmol) in 20 mL DMF for 5 min. The slurry was treated with sodium bis(trimethylsilyl)amide, 1.0M solution in tetrahydrofuran (2.66 mL, 2.66 mmol) rapidly via syringe, to give a dark blue solution. After 2 min, allyl iodide (0.306 mL, 3.32 mmol) was added via syringe, and the color gradually faded from blue to light brown. After 1 h, the reaction mixture was quenched with sat'd aq. NH4Cl and MTBE. The organic layer was washed with water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting oil was dissolved in DCM, adsorbed onto 7 g silica gel, dried, and purified by silica gel chromatography ISCO, 40 g, gradient, 0-50% EA/hexanes, to give 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(4-phenylocta-1,7-dien-4-yl)thiazolo[5,4-b]pyridine as a light yellow foam MS (ESI) m/z: Calculated: 500.2; Observed: 501.1 (M++1).

Workup

  1. customto give a dark blue solution
  2. waitAfter 1 h
  3. customthe reaction mixture was quenched with sat'd aq. NH4Cl and MTBE
  4. washThe organic layer was washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe resulting oil was dissolved in DCM
  9. customdried
  10. custompurified by silica gel chromatography ISCO, 40 g, gradient, 0-50% EA/hexanes

Sources & evidence

ORD record
ord-bd589779f203493d88979e23dce3aafd
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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