Trifluoroacetic acid → 6-benzyl-1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid trifluoroacetate

HRID 628337Notes

Reaction equation

HRID 628337 reaction equation
[CH3:1][C:2]1[N:6]2[C:7]3[CH:13]=[C:12]([C:14]([OH:16])=[O:15])[NH:11][C:8]=3[CH:9]=[CH:10][C:5]2=[N:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[OH-].[Na+].[C:33]([OH:39])([C:35]([F:38])([F:37])[F:36])=[O:34]>CN(C=O)C.CO.O.C(#N)C>[F:36][C:35]([F:38])([F:37])[C:33]([OH:39])=[O:34].[CH2:23]([N:11]1[C:8]2[CH:9]=[CH:10][C:5]3[N:6]([C:2]([CH3:1])=[N:3][N:4]=3)[C:7]=2[CH:13]=[C:12]1[C:14]([OH:16])=[O:15])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 1369631101-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid2×

Product 1

HCID 1181594706-benzyl-1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid trifluoroacetate

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

The mixture from Step 3 containing 1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid (0.298 g, 1.38 mmol) was mixed in DMF (6 mL) and acetonitrile (6 mL) and was treated with Cs2CO3 (1.8 g, 5.5 mmol) and was stirred for 10 minutes before the addition of benzyl bromide (0.30 mL, 2.5 mmol, Aldrich). The reaction was stirred overnight. Water was added and the product was extracted with three portions of EtOAc. The combined extracts were dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-10% MeOH in DCM, was used to purify the desired alkylated ester (265 mg). This was stirred with 1.0 M NaOH (10 mL, 10 mmol) and methanol (10 mL) overnight. Some TFA was used to aid in dissolving insolubles and the product was purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN and H2O containing 0.1% TFA). Yield: (44 mg, 7%). LCMS (M+H)+: 307.0.

Workup

  1. extractionthe product was extracted with three portions of EtOAc
  2. dry with materialThe combined extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. washFlash chromatography, eluting with a gradient from 0-10% MeOH in DCM
  6. customto purify the desired alkylated ester (265 mg)
  7. dissolutionin dissolving insolubles
  8. customthe product was purified via preparative HPLC-MS (C18
  9. washeluting with a gradient of MeCN and H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-9c7aa484b5274184ba58f5a808bcdce2
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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