3-Benzyl-5-chloro-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazine-2-carbaldehyde → 3-benzyl-5-chloro-2-(cyclopropyl-hydroxy-methyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one

HRID 1795977Notes

Reaction equation

HRID 1795977 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[CH2:6]([N:13]1[C:18](=[O:19])[C:17]2=[C:20]([Cl:23])[CH:21]=[CH:22][N:16]2[N:15]=[C:14]1[CH:24]=[O:25])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C(Cl)Cl>[CH2:6]([N:13]1[C:18](=[O:19])[C:17]2=[C:20]([Cl:23])[CH:21]=[CH:22][N:16]2[N:15]=[C:14]1[CH:24]([CH:1]1[CH2:3][CH2:2]1)[OH:25])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

4

Reactant 2

HCID 221800693-Benzyl-5-chloro-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazine-2-carbaldehydeHCID 178418630HCID 178418630, compound

Product 1

HCID 221800653-benzyl-5-chloro-2-(cyclopropyl-hydroxy-methyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-oneYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Cyclopropyl magnesium bromide (Boulder Scientific, 0.78 M, 8.92 ml, 6.96 mmol) was added dropwise to a −78° C. solution of 3-benzyl-5-chloro-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazine-2-carbaldehyde (1.0 g, 3.48 mmol) in CH2Cl2 (20 mL) over 45 min. The reaction mixture was stirred at −78° C. for 30 min, warmed to room temperature and quenched with saturated NH4Cl (100 mL). The reaction mixture was extracted with CHCl3 (3×75 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by reverse phase C-18 chromatography eluting over a 30 minute gradient with 45–90% aqueous methanol with 0.1% TFA to afford the title compound (0.54 g, 48%) as a solid: 1H NMR (DMF-d7) δ 7.68 (m, 1H), 7.26–7.38 (m, 5H), 6.71 (m, 1H), 6.28 (d, 1H, J=6.41 Hz), 5.71 (m, 1H), 5.28 (m, 1H), 3.86 (m, 1H), 1.46 (m, 1H), 0.57–0.59 (m, 1H), 0.38–0.46 (m, 2H), 0.13 (m, 1H); MS (ESI+) 330 (M++H); HRMS (ESI+) calculated: 330.1009 (M++H). found: 330.1000 (M++H).

Workup

  1. temperaturewarmed to room temperature
  2. customquenched with saturated NH4Cl (100 mL)
  3. extractionThe reaction mixture was extracted with CHCl3 (3×75 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by reverse phase C-18 chromatography
  8. washeluting over a 30 minute gradient with 45–90% aqueous methanol with 0.1% TFA

Sources & evidence

ORD record
ord-9f4550f246d64ef0a485335c54f7a9b3
Source dataset
uspto-grants-2006_04
Patent number
US07030118B2

Reaction notes

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