Triethylamine → 2-(((3-methyl-4-((8-methyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)methoxy)pyridin-2-yl)methyl)thio)-1H-benzimidazole

HRID 1645529ノート

反応式

HRID 1645529 の反応式
[CH3:1][C:2]1[C:3]([CH2:21]O)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1([CH3:20])[O:19][CH2:18][C:13]2([O:17][CH2:16][CH2:15][O:14]2)[CH2:12][O:11]1.C(N(CC)CC)C.CS(Cl)(=O)=O.C(=O)([O-])O.[Na+].[SH:40][C:41]1[NH:42][C:43]2[CH:49]=[CH:48][CH:47]=[CH:46][C:44]=2[N:45]=1.[OH-].[Na+]>C(OCC)(=O)C.C1COCC1>[CH3:1][C:2]1[C:3]([CH2:21][S:40][C:41]2[NH:45][C:44]3[CH:46]=[CH:47][CH:48]=[CH:49][C:43]=3[N:42]=2)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1([CH3:20])[O:19][CH2:18][C:13]2([O:17][CH2:16][CH2:15][O:14]2)[CH2:12][O:11]1

参加物

9

反応物 6

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 59792595(3-Methyl-4-((8-methyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)methoxy)pyridin-2-yl)methanolHCID 178527775HCID 178527775、化合物

生成物 1

HCID 597925332-(((3-methyl-4-((8-methyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)methoxy)pyridin-2-yl)methyl)thio)-1H-benzimidazole収率 85%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a THF (7 ml) solution of the (3-methyl-4-((8-methyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)methoxy)pyridin-2-yl)methanol (312 mg, 1.00 mmol) obtained in the step (5e), triethylamine (0.30 ml, 2.15 mmol) was added at room temperature, and then methanesulfonyl chloride (0.12 ml, 1.55 mmol) was added under cooling in an ice-salt bath and stirred for 30 minutes in the same conditions. To the reaction mixture, a saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate were added. The aqueous layer was extracted with ethyl acetate. Organic layers were combined, washed with water and a saline solution, dried over anhydrous sodium sulfate, and concentrated. The obtained residue was dissolved in ethanol (6 ml). To the resultant solution, 2-mercaptobenzimidazole (150 mg, 1.00 mmol) and sodium hydroxide (160 mg, 4.00 mmol) were added and stirred at room temperature for 16.5 hours. After the reaction mixture was concentrated, NH silica gel was added to the residue and the mixture was dried. The obtained crude product was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate=1/0, 1/1-0/1 gradient) and desired fractions were concentrated to obtain the title compound (377 mg, 85.0% yield) as a white foam.

後処理

  1. additionwas added at room temperature
  2. temperatureunder cooling in an ice-salt bath
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washwashed with water
  5. dry with materiala saline solution, dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. dissolutionThe obtained residue was dissolved in ethanol (6 ml)
  8. stirringstirred at room temperature for 16.5 hours
  9. concentrationAfter the reaction mixture was concentrated
  10. additionNH silica gel was added to the residue
  11. customthe mixture was dried
  12. customThe obtained crude product
  13. customwas purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate=1/0, 1/1-0/1 gradient)
  14. concentrationdesired fractions were concentrated

出典と根拠

ORDレコード
ord-9494575dca2f474f9ae0f2af3cc47ee1
出典データセット
uspto-grants-2012_02
特許番号
US08124780B2

反応ノート

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