Triethylamine → 2-(((4-(5,7-dioxaspiro[2.5]oct-6-ylmethoxy)-3-methylpyridin-2-yl)methyl)thio)-1H-benzimidazole

HRID 1645511Notes

Reaction equation

HRID 1645511 reaction equation
[CH2:1]1[C:3]2([CH2:8][O:7][CH:6]([CH2:9][O:10][C:11]3[CH:16]=[CH:15][N:14]=[C:13]([CH2:17]O)[C:12]=3[CH3:19])[O:5][CH2:4]2)[CH2:2]1.C(N(CC)CC)C.CS(Cl)(=O)=O.[SH:32][C:33]1[NH:34][C:35]2[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=2[N:37]=1>CO.O1CCCC1>[CH2:1]1[C:3]2([CH2:8][O:7][CH:6]([CH2:9][O:10][C:11]3[CH:16]=[CH:15][N:14]=[C:13]([CH2:17][S:32][C:33]4[NH:37][C:36]5[CH:38]=[CH:39][CH:40]=[CH:41][C:35]=5[N:34]=4)[C:12]=3[CH3:19])[O:5][CH2:4]2)[CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59792562(4-(5,7-Dioxaspiro[2.5]oct-6-ylmethoxy)-3-methylpyridin-2-yl)methanolHCID 178527775HCID 178527775, compound

Product 1

HCID 597924672-(((4-(5,7-dioxaspiro[2.5]oct-6-ylmethoxy)-3-methylpyridin-2-yl)methyl)thio)-1H-benzimidazoleYield 80.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-19 °C

Procedure

The (4-(5,7-dioxaspiro[2.5]oct-6-ylmethoxy)-3-methylpyridin-2-yl)methanol (520 mg, 1.96 mmol) obtained in the step (2d) was mixed with triethylamine (1.09 ml, 7.84 mmol) and tetrahydrofuran (10 ml) and the resultant mixture was cooled to −19° C. Methanesulfonyl chloride (228 μl, 2.94 mmol) was added to the mixture, which was stirred at −19° C. for 30 minutes. In the same conditions, 2-mercaptobenzimidazole (324 mg, 2.16 mmol) was added to the reaction mixture. After the reaction mixture was stirred at room temperature for 2 days, methanol and NH silica gel were added to the mixture, and the solvent was distilled off. The mixture of the reaction mixture and NH silica gel was purified by silica gel column chromatography (silica gel: 80 g, elution solvent: ethyl acetate/heptane=4/6 to 7/3→methanol/ethyl acetate=1/9) to obtain the title compound (629 mg, yield: 80.7%) as a colorless foam.

Workup

  1. stirringAfter the reaction mixture was stirred at room temperature for 2 days
  2. distillationthe solvent was distilled off
  3. additionThe mixture of the reaction mixture and NH silica gel
  4. customwas purified by silica gel column chromatography (silica gel: 80 g, elution solvent: ethyl acetate/heptane=4/6 to 7/3→methanol/ethyl acetate=1/9)

Sources & evidence

ORD record
ord-17b9369bb75d4a309ab23e7ba8b97584
Source dataset
uspto-grants-2012_02
Patent number
US08124780B2

Reaction notes

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