Tetrahydrofuran → 2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-phenylpent-4-enyl)thiazolo[5,4-b]pyridine

HRID 1177430Notes

Reaction equation

HRID 1177430 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]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:16]=3)=[C:9]([F:29])[CH:8]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:40]1[CH2:44]O[CH2:42][CH2:41]1.BrCCC=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]([CH:22]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:42][CH2:41][CH:40]=[CH2:44])[N:16]=3)=[C:9]([F:29])[CH:8]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 21241Homoallyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 591748722-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-benzylthiazolo[5,4-b]pyridine

Product 1

HCID 686359872-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-phenylpent-4-enyl)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-benzylthiazolo[5,4-b]pyridine (1.00 g, 2.46 mmol) in 20 mL DMF for 5 min. To the rapidly stirring reaction mixture was added LiHMDS 1.0M in THF (2.71 mL, 2.71 mmol) rapidly dropwise. The resulting deep blue reaction mixture was stirred for 2 min, at which point 4-bromo-1-butene (0.499 mL, 4.92 mmol) was added rapidly via syringe. The color of the reaction slowly became purple over 5 min, then brown over about 10-15 min additional. After 1.5 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 to give 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-phenylpent-4-enyl)thiazolo[5,4-b]pyridine as an orange solid MS (ESI) m/z: Calculated: 460.2; Observed: 461.1 (M++1).

Workup

  1. customreaction mixture
  2. customThe resulting deep blue reaction mixture
  3. additionwas added rapidly via syringe
  4. customThe color of the reaction slowly became purple over 5 min
  5. waitAfter 1.5 h
  6. customthe reaction mixture was quenched with sat'd aq. NH4Cl and MTBE
  7. washThe organic layer was washed with water, brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8130528c5699496f8d40d868437c87fb
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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