Tetrahydrofuran → 7-Bromo-4-chloro-2-(methylthio)pyrrolo[2,1-f][1,2,4]triazine

HRID 1261921Notes

Reaction equation

HRID 1261921 reaction equation
[Cl:1][C:2]1[C:7]2=[CH:8][CH:9]=[CH:10][N:6]2[N:5]=[C:4]([S:11][CH3:12])[N:3]=1.O1CCCC1.[Br:18]N1C(=O)CCC1=O>CO>[Br:18][C:10]1[N:6]2[C:7]([C:2]([Cl:1])=[N:3][C:4]([S:11][CH3:12])=[N:5]2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 67184N-bromobutanimideHCID 378183844-Chloro-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 580713637-Bromo-4-chloro-2-(methylthio)pyrrolo[2,1-f][1,2,4]triazine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Into a Round bottom flask, [A] 4-Chloro-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (25.47 g, 0.1276 mol), Tetrahydrofuran (1000 mL), and Methanol (640 mL) were added. N-Bromosuccinimide (22.7 g, 0.128 mol) was added portionwise to the reaction for 1 hour at 0° C. The reaction was stirred at room temperature for 1 hour and the solvent was removed under vacuum. The solid was partitioned with water and DCM (500 mL). The organic was separated, washed with Brine, and dried over magnesium sulfate. The solid was filtered and washed with DCM. The filtrate was then reduced under vacuum to afford 7-Bromo-4-chloro-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine as a yellow solid. 7-Bromo-4-chloro-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine was suspended in Isopropyl alcohol (410 mL) at 55° C. Sodium borohydride (10.1 g, 0.268 mol) was added and heated at 60° C. for 3 hours. The reaction was allowed to cool to RT. The solid was filtered and washed with DCM. The solvent was partially removed to ensure the intermediate stayed in solution. (The intermediate is not stable out of solution). Methylene chloride (800 mL) was added to the viscous oil. Dichlorodicyanoquinone (31.8 g, 0.140 mol) was then added portion wise over 15 minutes. The mixture was stirred for 30 minutes. The solid was filtered through Celite, washed with DCM and the filtrate was removed under vacuum. The crude reaction mixture was purified via ISCO column chromatography with hexane and EtOAc as an eluant (0 to 8% EtOAc). The collected fractions afforded 12.2 grams of 7-Bromo-4-chloro-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine as a light yellow solid. 1H NMR (400 MHz, DMSO, d6) δ 8.95 (s, 1H), 7.09 (s, 2H), 2.55 (s, 3H).

Workup

  1. customthe solvent was removed under vacuum
  2. customThe solid was partitioned with water and DCM (500 mL)
  3. customThe organic was separated
  4. washwashed with Brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationThe solid was filtered
  7. washwashed with DCM

Sources & evidence

ORD record
ord-17348f33a87d4c55b9454fddeddaa76e
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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