Cesium carbonate → 2-(4-(1,3-Dioxan-2-yl)-3,5-dimethylphenyl)-5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine

HRID 1177451Notes

Reaction equation

HRID 1177451 reaction equation
[C:1]1([C:7]2([C:10]3[N:15]=[C:14]4[S:16][CH:17]=[N:18][C:13]4=[CH:12][CH:11]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:20]1[CH:25]=[C:24]([CH3:26])[C:23]([CH:27]2[O:32][CH2:31][CH2:30][CH2:29][O:28]2)=[C:22]([CH3:33])[CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[O:28]1[CH2:29][CH2:30][CH2:31][O:32][CH:27]1[C:23]1[C:22]([CH3:33])=[CH:21][C:20]([C:17]2[S:16][C:14]3[C:13]([N:18]=2)=[CH:12][CH:11]=[C:10]([C:7]2([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH2:8][CH2:9]2)[N:15]=3)=[CH:25][C:24]=1[CH3:26]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 591748745-(1-Phenylcyclopropyl)thiazolo[5,4-b]pyridineHCID 591748982-(4-Bromo-2,6-dimethylphenyl)-1,3-dioxane

Product 1

HCID 671115052-(4-(1,3-Dioxan-2-yl)-3,5-dimethylphenyl)-5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
190 °C

Procedure

A mixture of 5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (23.2 mg, 92 μmol), 2-(4-bromo-2,6-dimethylphenyl)-1,3-dioxane (25 mg, 92 μmol), PdCl2(AmPhos)2 (4.8 mg, 7.7 μmol), and cesium carbonate (90 mg, 276 μmol) in DMF (1.0 mL) was heated (microwave) at 190° C. under argon for 30 min, then at 200° C. for 30 min. The reaction mixture was then partitioned between EtOAc (40 mL) and water (10 mL). The organic layer was separated and sequentially washed with water (2×10 mL) and brine (10 mL), then dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-70% EtOAc/Hex,) furnished 2-(4-(1,3-dioxan-2-yl)-3,5-dimethylphenyl)-5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine as a yellow solid. MS (ESI) m/z: Calculated: 442.2; Observed: 443.2 (M++1).

Workup

  1. customThe reaction mixture was then partitioned between EtOAc (40 mL) and water (10 mL)
  2. customThe organic layer was separated
  3. washsequentially washed with water (2×10 mL) and brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customChromatographic purification of the residue (silica gel, 0-70% EtOAc/Hex,)

Sources & evidence

ORD record
ord-efe6b844e004412b951aa10b3e520793
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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