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

HRID 656637Notes

Reaction equation

HRID 656637 reaction equation
[CH:1]1([NH:4][C:5](=[O:8])[CH2:6][SH:7])[CH2:3][CH2:2]1.C[O-].[Na+].Cl[C:13]1[N:20]=[C:19]([O:21][CH2:22][CH2:23][O:24][CH3:25])[C:18]([Cl:26])=[C:17]([CH3:27])[C:14]=1[C:15]#[N:16].ClC1C(Cl)=NC(OCCOC)=C(C=1C)C#N>CO.CCOC(C)=O.CCCCCC.O>[CH:1]1([NH:4][C:5]([C:6]2[S:7][C:13]3=[N:20][C:19]([O:21][CH2:22][CH2:23][O:24][CH3:25])=[C:18]([Cl:26])[C:17]([CH3:27])=[C:14]3[C:15]=2[NH2:16])=[O:8])[CH2:3][CH2:2]1

Participants

9

Reactant 4

HCID 10942334Sodium MethoxideHCID 55207200N-cyclopropyl-2-mercaptoacetamideHCID 862419192,5-Dichloro-6-(2-methoxy-ethoxy)-4-methyl-nicotinonitrileHCID 862419205,6-Dichloro-2-(2-methoxy-ethoxy)-4-methyl-nicotinonitrile

Product 1

HCID 576644023-Amino-5-chloro-6-(2-methoxy-ethoxy)-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamideYield 10%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-cyclopropyl-2-mercapto-acetamide (0.452 g, 3.45 mmol) in MeOH (5 ml) is added sodium methoxide solution (25% wt. in MeOH)(0.589 ml, 2.58 mmol). The resulting solution is stirred at room temperature for 30 minutes, then treated with a 1:1 mixture of 2,5-dichloro-6-(2-methoxy-ethoxy)-4-methyl-nicotinonitrile and 5,6-dichloro-2-(2-methoxy-ethoxy)-4-methyl-nicotinonitrile (0.450 g, 1.72 mmol). The reaction vessel is sealed, heated at 100° C. for 2.5 hours, and cooled to room temperature. The reaction mixture is poured over water (60 ml), then extracted with EtOAc (2×40 ml). The combined organic layers are washed with brine (50 ml), dried (anhydrous magnesium sulfate), filtered, and concentrated to give a yellow-brown solid. Flash chromatography (1.5:1 hexane:EtOAc) affords the title compound as a cream colored solid (53 mg, 10%). Mass (m/z): 356.1 (M++1).

Workup

  1. customThe reaction vessel is sealed
  2. temperatureheated at 100° C. for 2.5 hours
  3. temperaturecooled to room temperature
  4. extractionextracted with EtOAc (2×40 ml)
  5. washThe combined organic layers are washed with brine (50 ml)
  6. dry with materialdried (anhydrous magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a yellow-brown solid

Sources & evidence

ORD record
ord-26d57cb50d7448daac1083dd745d1275
Source dataset
uspto-grants-2011_12
Patent number
US08071776B2

Reaction notes

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