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

HRID 628298Notes

Reaction equation

HRID 628298 reaction equation
[CH3:1][C:2]1[N:6]2[C:7]3[CH:13]=[C:12]([C:14]([OH:16])=[O:15])[N:11](S(C4C=CC=CC=4)(=O)=O)[C:8]=3[CH:9]=[CH:10][C:5]2=[N:4][N:3]=1.[OH-].[Na+].C([O-])([O-])=O.[K+].[K+].[CH2:34](Br)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C1COCC1.CO.O>[CH2:34]([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:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

8

Reactant 4

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 1181597591-methyl-6-(phenylsulfonyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid

Product 1

HCID 1181594716-benzyl-1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acidYield 37.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1-methyl-6-(phenylsulfonyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid (0.106 g, 0.297 mmol, from Step 3) in THF (2 mL) and methanol (2 mL) was added 1.0 M NaOH (2 mL, 2 mmol) and the reaction was stirred for 1 hour. The reaction was diluted with methanol and was purified by preparative HPLC-MS (C18 eluting with a gradient of MeCN and H2O containing 0.15% NH4OH). The eluent was evaporated and the resulting solid was dissolved in DMF (3 mL). K2CO3 (0.16 g, 1.2 mmol) followed by benzyl bromide (0.053 mL, 0.45 mmol) were added and the reaction was stirred overnight. The reaction was diluted with water and extracted with three portions of ethyl acetate. The combined extracts were washed with water, then brine, dried over sodium sulfate, filtered and concentrated. The residue was stirred with 1.0 N NaOH (2 mL) in THF (2 mL) and MeOH (2 mL) for 1 hour. Purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN and H2O containing 0.15% NH4OH) afforded product (34 mg, 37%). 1H NMR (300 MHz, CD3OD) δ 7.62 (dd, J=9.8, 0.7 Hz, 1H), 7.44 (d, J=0.6 Hz, 1H), 7.29 (d, J=9.8 Hz, 1H), 7.26-7.08 (m, 5H), 6.15 (s, 2H), 2.99 (s, 3H). LCMS (M+H)+: 307.1.

Workup

  1. customwas purified by preparative HPLC-MS (C18
  2. washeluting with a gradient of MeCN and H2O containing 0.15% NH4OH)
  3. customThe eluent was evaporated
  4. dissolutionthe resulting solid was dissolved in DMF (3 mL)
  5. additionwere added
  6. stirringthe reaction was stirred overnight
  7. extractionextracted with three portions of ethyl acetate
  8. washThe combined extracts were washed with water
  9. dry with materialbrine, dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. stirringThe residue was stirred with 1.0 N NaOH (2 mL) in THF (2 mL) and MeOH (2 mL) for 1 hour
  13. customPurified via preparative HPLC-MS (C18
  14. washeluting with a gradient of MeCN and H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-d802e84661c84b3bb61927d8800d6edb
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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