Tetrahydrofuran → [3-chloro-6'-(6-morpholin-4-yl-1H-benzoimidazol-2-yl)-[2,3]bipyridinyl-5-yl]-methanol

HRID 2089125Notes

Reaction equation

HRID 2089125 reaction equation
[Cl:1][C:2]1[C:3]([C:11]2[CH:12]=[N:13][C:14]([C:17]3[NH:21][C:20]4[CH:22]=[C:23]([N:26]5[CH2:31][CH2:30][O:29][CH2:28][CH2:27]5)[CH:24]=[CH:25][C:19]=4[N:18]=3)=[CH:15][CH:16]=2)=[N:4][CH:5]=[C:6]([C:8](O)=[O:9])[CH:7]=1.O1CCCC1.[OH-].[Al+3].[Li+].[OH-].[OH-].[OH-]>O>[Cl:1][C:2]1[C:3]([C:11]2[CH:12]=[N:13][C:14]([C:17]3[NH:21][C:20]4[CH:22]=[C:23]([N:26]5[CH2:27][CH2:28][O:29][CH2:30][CH2:31]5)[CH:24]=[CH:25][C:19]=4[N:18]=3)=[CH:15][CH:16]=2)=[N:4][CH:5]=[C:6]([CH2:8][OH:9])[CH:7]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 16206110Aluminate (Al(OH)41-), lithium, (T-4)-HCID 250604343-chloro-6'-(6-morpholin-4-yl-1H-benzoimidazol-2-yl)-[2,3]bipyridinyl-5-carboxylic acid

Product 1

HCID 25060936[3-chloro-6'-(6-morpholin-4-yl-1H-benzoimidazol-2-yl)-[2,3]bipyridinyl-5-yl]-methanolYield 93%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-80 °C

Procedure

0.49 g of 3-chloro-6′-(6-morpholin-4-yl-1H-benzoimidazol-2-yl)-[2,3′]bipyridinyl-5-carboxylic acid (71) (1.12 mmol) prepared in Example 58 was added to 5 mL of tetrahydrofuran, and cooled to −80° C. 0.09 g of lithium aluminum hydroxide (2.24 mmol) was slowly added thereto. After stirring for 2 hours, the temperature of the reactant was slowly raised to room temperature, and further reacted 2 hours. A small amount of water was added thereto terminate the reaction, and concentrated under reduced pressure. Then, the resultant was dissolved in ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluting solvent: chloroform/methanol=20/1) to obtain 0.44 g of yellow crystal, [3-chloro-6′-(6-morpholin-4-yl-1H-benzoimidazol-2-yl)-[2,3′]bipyridinyl-5-yl]-methanol compound (yield 93%).

Workup

  1. temperaturethe temperature of the reactant was slowly raised to room temperature
  2. customfurther reacted 2 hours
  3. customthereto terminate
  4. customthe reaction
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThen, the resultant was dissolved in ethyl acetate
  7. washwashed with water
  8. dry with materialThe organic layer was dried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was separated by column chromatography (eluting solvent: chloroform/methanol=20/1)

Sources & evidence

ORD record
ord-b4c09169a6b44a1a97121a50865de74d
Source dataset
uspto-grants-2013_05
Patent number
US08436022B2

Reaction notes

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