Methyl Glycolate → (3-Amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid methylester

HRID 656641Notes

Reaction equation

HRID 656641 reaction equation
[C:1]([O:5][CH3:6])(=[O:4])[CH2:2][OH:3].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH:17]1([NH:20][C:21]([C:23]2[S:36][C:26]3=[N:27][C:28](S(C)=O)=[C:29]([Cl:32])[C:30]([CH3:31])=[C:25]3[C:24]=2[NH2:37])=[O:22])[CH2:19][CH2:18]1>C1COCC1>[CH3:6][O:5][C:1](=[O:4])[CH2:2][O:3][C:28]1[N:27]=[C:26]2[S:36][C:23]([C:21](=[O:22])[NH:20][CH:17]3[CH2:18][CH2:19]3)=[C:24]([NH2:37])[C:25]2=[C:30]([CH3:31])[C:29]=1[Cl:32]

Participants

5

Reactant 3

HCID 66774Methyl GlycolateHCID 2733832Lithium HexamethyldisilazideHCID 576644203-Amino-5-chloro-6-methanesulfinyl-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

Product 1

HCID 68436041(3-Amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid methylesterYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl glycolate (6.55 g, 72.7 mmol) in THF (35 ml) at room temperature is added dropwise a solution of lithium bis(trimethylsilyl)amide (1.0 M in hexanes) (36.35 ml, 36.35 mmol). The resulting mixture is stirred for 20 minutes, then treated with 3-amino-5-chloro-6-methanesulfinyl-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide (5.0 g, 14.54 mmol). The reaction vessel is sealed and heated at 90° C. for 3 hours. The reaction is cooled to room temperature and quenched by the addition of water (50 ml). The mixture is partitioned between water and EtOAc (250 ml each), and the layers are shaken and separated. The aqueous layer is extracted with 2×100 ml of EtOAc. The combined organic layers are dried (anhydrous magnesium sulfate), filtered, concentrated, and flashed (1:1 hexane:EtOAc) to give the title compound as a yellow solid (3.1 g, 58%). Mass (m/z): 370.1 (M++1), 368.0 (M+−1).

Workup

  1. customThe reaction vessel is sealed
  2. temperatureThe reaction is cooled to room temperature
  3. customquenched by the addition of water (50 ml)
  4. customThe mixture is partitioned between water and EtOAc (250 ml each)
  5. stirringthe layers are shaken
  6. customseparated
  7. extractionThe aqueous layer is extracted with 2×100 ml of EtOAc
  8. dry with materialThe combined organic layers are dried (anhydrous magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-de10177793ed460f83bf00d503c70af6
Source dataset
uspto-grants-2011_12
Patent number
US08071776B2

Reaction notes

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