Triethylamine → HCID 21094055, compound

HRID 1350323Notes

Reaction equation

HRID 1350323 reaction equation
CCN(CC)CC.I[CH2:9][CH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.[SH:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]([CH2:32][CH:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)[C:24]([NH:26][C:27]2[S:28][CH:29]=[CH:30][N:31]=2)=[O:25])=[CH:19][CH:18]=1>CN(C=O)C>[O:36]1[CH2:37][CH2:38][CH:33]([CH2:32][CH:23]([C:20]2[CH:21]=[CH:22][C:17]([S:16][CH2:9][CH:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)=[CH:18][CH:19]=2)[C:24]([NH:26][C:27]2[S:28][CH:29]=[CH:30][N:31]=2)=[O:25])[CH2:34][CH2:35]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27955074-(Iodomethyl)oxaneHCID 21093996HCID 21093996, compound

Product 1

HCID 21094055HCID 21094055, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution of 2-(4-methoxymethylsulfanylphenyl)-3-(tetrahydropyran-4-yl)-N-thiazol-2-ylpropionamide (EXAMPLE 77, 1.29 g, 3.28 mmol) in THF (50 mL) was added to a stirred solution of AgNO3 (0.59 g, 3.28 mmol) in EtOH (85 mL) at 40° C. The mixture was protected from light and stirred at 40° C. for 21 h. The solvents were evaporated off under reduced pressure, then the remaining solid was triturated with i-PrOH (60 mL), THF (60 mL), and Et2O (60 mL). After air-drying, the solid was stirred vigorously with CH2Cl2 (200 mL) and 6M HCl (82 mL) for 4 h under Ar. The layers were separated, then the aqueous phase was extracted with CH2Cl2 (2×100 mL). The combined organic extracts were filtered through Celite, washed with brine (100 mL) and dried (MgSO4). Filtration and solvent evaporation furnished 2-(4-mercaptophenyl)-3-(tetrahydropyran-4-yl)-N-thiazol-2-ylpropionamide: m/z (ES+)=349.2 [M+H]+. NEt3 (0.14 mL, 1006 μmol) and a solution of 4-iodomethyltetrahydropyran (151 mg, 668 μmol) in anhydrous DMF (3 mL) were added to a stirred solution of this benzenethiol (197 mg, 565 μmol) in anhydrous DMF (7 mL) at 0° C. The mixture was warmed to 20° C., before being stirred for 16 h. The solvents were evaporated off under reduced pressure, then the residue was partitioned between CH2Cl2 (25 mL) and 2% aqueous citric acid (10 mL). The aqueous layer was extracted with CH2Cl2 (10 mL), then the combined organic layers were washed with H2O (10 mL), saturated aqueous Na2CO3 (10 mL), H2O (10 mL), and brine (10 mL). After drying (MgSO4), filtration and solvent evaporation gave a residue that was subjected to flash chromatography (IH-EtOAc, 3:1 to 0:1) to furnish the title compound: RTA=3.61 min; m/z (ES+)=447.3 [M+H]+.

Workup

  1. customThe solvents were evaporated off under reduced pressure
  2. customthe residue was partitioned between CH2Cl2 (25 mL) and 2% aqueous citric acid (10 mL)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (10 mL)
  4. washthe combined organic layers were washed with H2O (10 mL), saturated aqueous Na2CO3 (10 mL), H2O (10 mL), and brine (10 mL)
  5. customAfter drying
  6. filtration(MgSO4), filtration and solvent evaporation
  7. customgave a residue that

Sources & evidence

ORD record
ord-366a5d79204f47cfaaa2ca22a85acada
Source dataset
uspto-grants-2007_05
Patent number
US07214681B2

Reaction notes

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