Chlorotrimethylsilane → 1-(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)cyclohexanol

HRID 578758Notes

Reaction equation

HRID 578758 reaction equation
Br[C:2]1[N:10]2[C:5]([C:6]([NH2:11])=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.Cl[Si](C)(C)C.CC([Mg]Cl)C.[C:22]1(=[O:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>C1COCC1>[NH2:11][C:6]1[C:5]2=[CH:4][CH:3]=[C:2]([C:22]3([OH:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[N:10]2[N:9]=[CH:8][N:7]=1

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 7967CyclohexanoneHCID 422813837-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amineHCID 178418918HCID 178418918, compound

Product 1

HCID 711871071-(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)cyclohexanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

7-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (1.20 g, 5.63 mmol) was dissolved in THF (25 mL) under argon at room temperature. Chlorotrimethylsilane (1.43 mL, 11.27 mmol) was added, and the mixture was stirred at room temperature for 3 h. Then, it was cooled to 0° C., 2-propyl magnesium chloride (11.8 mL of a 2.0 M solution in THF, 23.7 mmol) was added, and stirring was maintained for another 3 h while the reaction mixture was allowed to warm to room temperature. Then, cyclohexanone (0.88 mL, 8.45 mmol) was added, and stirring was continued for 16 h. The reaction was quenched with a mixture (1:1) of concentrated aqueous ammonium chloride solution and ice until the pH reached 6-7. The mixture was extracted with two portions of ethyl acetate, and the combined organic extracts were dried over anhydrous sodium carbonate and concentrated to dryness. The product thus obtained was used without further purification (purity 68% by HPLC). Yield: 1.87 g (97% of th.).

Workup

  1. temperatureThen, it was cooled to 0° C.
  2. stirringstirring
  3. temperaturewas maintained for another 3 h while the reaction mixture
  4. temperatureto warm to room temperature
  5. stirringstirring
  6. waitwas continued for 16 h
  7. customThe reaction was quenched with a mixture (1:1) of concentrated aqueous ammonium chloride solution and ice until the pH
  8. extractionThe mixture was extracted with two portions of ethyl acetate
  9. dry with materialthe combined organic extracts were dried over anhydrous sodium carbonate
  10. concentrationconcentrated to dryness
  11. customThe product thus obtained
  12. customwas used without further purification (purity 68% by HPLC)

Sources & evidence

ORD record
ord-8c036f9e94ec4de984f300573a86f9ca
Source dataset
uspto-grants-2015_05
Patent number
US09040691B2

Reaction notes

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