Hexane → 3-Amino-5-chloro-6-(2-hydroxy-ethoxy)-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

HRID 656642Notes

Reaction equation

HRID 656642 reaction equation
C[O:2][C:3](=O)[CH2:4][O:5][C:6]1[N:11]=[C:10]2[S:12][C:13]([C:16](=[O:21])[NH:17][CH:18]3[CH2:20][CH2:19]3)=[C:14]([NH2:15])[C:9]2=[C:8]([CH3:22])[C:7]=1[Cl:23].[H-].C([Al+]CC(C)C)C(C)C.CCOC(C)=O.CCCCCC>C1COCC1>[CH:18]1([NH:17][C:16]([C:13]2[S:12][C:10]3=[N:11][C:6]([O:5][CH2:4][CH2:3][OH:2])=[C:7]([Cl:23])[C:8]([CH3:22])=[C:9]3[C:14]=2[NH2:15])=[O:21])[CH2:20][CH2:19]1

Participants

6

Reactant 4

HCID 8058Hexane2×HCID 8857Ethyl Acetate2×HCID 21225700Diisobutylaluminumhydride2×HCID 68436041(3-Amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid methylester

Product 1

HCID 576644143-Amino-5-chloro-6-(2-hydroxy-ethoxy)-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamideYield 67.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (3-amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid methylester (0.250 g, 0.676 mmol) in THF (3 ml) at −78° C. is added dropwise a solution of diisobutylaluminum hydride (1.5M in toluene)(1.35 ml, 2.03 mmol). The reaction solution is stirred at −78° C. for 30 minutes, then room temperature for 1 hour. If the reaction is not complete, according to TLC (2:1 EtOAc:hexane), an additional 1.0 eq of diisobutylaluminum hydride (1.5M in toluene)(0.45 ml, 0.676 mmol) may be added. After 15 minutes, the reaction is quenched by the addition of 3 ml of a 1:1 mixture of MeOH:water. The reaction mixture is partitioned between water and EtOAc (50 ml each), and the layers are shaken and separated. The aqueous layer is extracted with 2×50 ml of EtOAc, and the combined organic layers are dried (anhydrous magnesium sulfate), filtered, and concentrated to give a yellow solid. This solid is taken up in 2:1 EtOAc:hexane, and once dissolved, a yellow precipitate is formed. The yellow solid is collected by filtration and dried in the vacuum oven at 60° C. overnight to afford the title compound as a yellow solid (0.155 g, 67%). Mass (m/z): 342.1 (M++1).

Workup

  1. waitroom temperature for 1 hour
  2. waitAfter 15 minutes
  3. customthe reaction is quenched by the addition of 3 ml of a 1:1 mixture of MeOH
  4. customThe reaction mixture is partitioned between water and EtOAc (50 ml each)
  5. stirringthe layers are shaken
  6. customseparated
  7. extractionThe aqueous layer is extracted with 2×50 ml of EtOAc
  8. dry with materialthe combined organic layers are dried (anhydrous magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a yellow solid
  12. customa yellow precipitate is formed
  13. filtrationThe yellow solid is collected by filtration
  14. customdried in the vacuum oven at 60° C. overnight

Sources & evidence

ORD record
ord-9ce4f38d6f8446c298b447d41ca485ed
Source dataset
uspto-grants-2011_12
Patent number
US08071776B2

Reaction notes

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