1,3-Dibromopropane → N-[3-(5-methyl-4-phenoxy-pyrrolo[2,1-f][1,2,4]triazin-6-yloxy)-propyl]-methanesulfonamide

HRID 984871Notes

Reaction equation

HRID 984871 reaction equation
[O:1]([C:8]1[C:13]2=[C:14]([CH3:18])[C:15]([OH:17])=[CH:16][N:12]2[N:11]=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:20][CH2:21][CH2:22]Br.C([O-])([O-])=O.[K+].[K+].[CH3:30][S:31]([NH2:34])(=[O:33])=[O:32]>CN(C=O)C.ClCCl>[CH3:18][C:14]1[C:15]([O:17][CH2:20][CH2:21][CH2:22][NH:34][S:31]([CH3:30])(=[O:33])=[O:32])=[CH:16][N:12]2[C:13]=1[C:8]([O:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[N:9][CH:10]=[N:11]2

Participants

7

Reactant 4

HCID 80011,3-DibromopropaneHCID 11430Potassium Carbonate2×HCID 72879MethanesulfonamideHCID 219458735-Methyl-4-phenoxypyrrolo[2,1-f][1,2,4]triazin-6-ol

Product 1

HCID 22508873N-[3-(5-methyl-4-phenoxy-pyrrolo[2,1-f][1,2,4]triazin-6-yloxy)-propyl]-methanesulfonamideYield 81%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-phenoxy-5-methyl-6-hydroxypyrrolo-[2,1-f][1,2,4]triazine (1.05 g, 4.35 mmol), 1,3-dibromopropane (4.0 g, 20 mmol), and K2CO3 (3 g, 22 mmol) was heated at 70° C. for 2 h. The solvent was removed in vacuo. The residue was purified by flash column chromatography (silica gel, eluting from dichloromethane to 20% ethyl acetate/dichloromethane) to afford the crude intermediate (1.35 g, 86% yield). This intermediate (1.3 g, 3.59 mmol) was heated with methanesulfonamide (2.0 g, 21 mmol) and K2CO3 (4 g, 29 mmol) in DMF (15 mL) for 2 h. The mixture was cooled, diluted with dichloromethane, washed twice with 5% Na2CO3 solution, dried and concentrated. The residue was purified by flash column chromatography (silica gel, 20% ethyl acetate/dichloromethane) to afford N-[3-(5-methyl-4-phenoxy-pyrrolo[2,1-f][1,2,4]triazin-6yloxy)-propyl]-methanesulfonamide (1.1 g, 81%) as a white solid. MS: (M+H)+=377.

Workup

  1. customThe solvent was removed in vacuo
  2. customThe residue was purified by flash column chromatography (silica gel, eluting from dichloromethane to 20% ethyl acetate/dichloromethane)
  3. customto afford the crude intermediate (1.35 g, 86% yield)
  4. temperatureThe mixture was cooled
  5. washwashed twice with 5% Na2CO3 solution
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography (silica gel, 20% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-db429ea5baf94eb9b989b4e33f870115
Source dataset
uspto-grants-2005_03
Patent number
US06869952B2

Reaction notes

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