Sodium hydride → 3-Amino-1-(4-methoxy-benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

HRID 2264907Notes

Reaction equation

HRID 2264907 reaction equation
[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[C:15]#[N:16])=[CH:5][CH:4]=1.Br[CH2:20][C:21]([O:23][CH3:24])=[O:22].[H-].[Na+]>CN(C=O)C>[CH3:24][O:23][C:21]([C:20]1[N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:18][CH:17]=2)[C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[C:15]=1[NH2:16])=[O:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 595966574-(4-Methoxy-benzylamino)-nicotinonitrile

Product 1

HCID 672120873-Amino-1-(4-methoxy-benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A cooled (0° C.) solution of 4-(4-methoxybenzylamino)-3-cyanopyridine (800 mg, 3.34 mmol) and methyl bromoacetate (0.37 mL, 4.02 mmol) in DMF was treated with sodium hydride (60% w/w in oil, 161 mg, 4.02 mmol) portionwise over 15 minutes. The mixture was allowed to warm to ambient temperature and stirred for 15 hours. The reaction was quenched by the addition of saturated ammonium chloride solution (10 mL) and the solvent evaporated. The resultant residue was partitioned between EtOAc (100 mL), water (50 mL) and saturated NaHCO3 solution (5 mL). The organic phase was dried (Na2SO4), filtered and evaporated to give a brown oil. The oil was purified by flash column chromatography (Si-PPC, DCM:MeOH, gradient 100:0 to 85:15) to provide the title compound as an off white solid (401 mg, 39%). LCMS (method B): RT=1.33 min, M+H+=312.

Workup

  1. customThe reaction was quenched by the addition of saturated ammonium chloride solution (10 mL)
  2. customthe solvent evaporated
  3. customThe resultant residue was partitioned between EtOAc (100 mL), water (50 mL) and saturated NaHCO3 solution (5 mL)
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give a brown oil
  8. customThe oil was purified by flash column chromatography (Si-PPC, DCM:MeOH, gradient 100:0 to 85:15)

Sources & evidence

ORD record
ord-f6b37374c9834340a35c880daee417ea
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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