Pyridine → 3-benzyl-5-chloro-2-(chloro-cyclopropyl-methyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one

HRID 1795978Notes

Reaction equation

HRID 1795978 reaction equation
S(Cl)([Cl:3])=O.[CH2:5]([N:12]1[C:17](=[O:18])[C:16]2=[C:19]([Cl:22])[CH:20]=[CH:21][N:15]2[N:14]=[C:13]1[CH:23]([CH:25]1[CH2:27][CH2:26]1)O)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.N1C=CC=CC=1>C(Cl)Cl>[CH2:5]([N:12]1[C:17](=[O:18])[C:16]2=[C:19]([Cl:22])[CH:20]=[CH:21][N:15]2[N:14]=[C:13]1[CH:23]([Cl:3])[CH:25]1[CH2:27][CH2:26]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 221800653-benzyl-5-chloro-2-(cyclopropyl-hydroxy-methyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one

Product 1

HCID 221800283-benzyl-5-chloro-2-(chloro-cyclopropyl-methyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-oneYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Thionyl chloride (2 M in CH2Cl2, 1.52 ml, 3.04 mmol) was added to solution of 3-benzyl-5-chloro-2-(cyclopropyl-hydroxy-methyl)-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one (0.5 g, 1.52 mmol) and pyridine (0.49 mL, 6.08 mmol) in CH2Cl2 (10 ml) at 0° C. The reaction mixture was stirred at 0° C. for 45 min and then quenched by pouring on to ice. The solution was treated with 1 N HCl (100 mL) and extracted with CHCl3 (3×100 mL). The combined organic extracts were washed with saturated NaHCO3 (100 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with 4/1 hexane/EtOAc to afford the title compound (0.368 g, 70%) as a solid: 1H NMR (DMF-d7) δ 7.96 (m, 1H), 7.47–7.60 (m, 5H), 6.97 (m, 1H), 5.94 (m, 1H), 5.22 (m, 1H), 4.63 (d, 1H, J=9.99 Hz), 2.09–2.12 (m, 1H), 0.98–1.05 (m, 1H), 0.86–0.97 (m, 1H), 0.68–0.71 (m, 1H), 0.23–0.27 (m, 1H); MS (ESI+) 348 (M++H), HRMS (ESI+) calculated: 348.0670 (M++H). found: 348.0686 (M++H).

Workup

  1. customquenched
  2. additionby pouring on to ice
  3. additionThe solution was treated with 1 N HCl (100 mL)
  4. extractionextracted with CHCl3 (3×100 mL)
  5. washThe combined organic extracts were washed with saturated NaHCO3 (100 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography on silica gel eluting with 4/1 hexane/EtOAc

Sources & evidence

ORD record
ord-b712e15772c1451893aa953d5a7e5c3a
Source dataset
uspto-grants-2006_04
Patent number
US07030118B2

Reaction notes

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