Chlorotrimethylsilane → Tert-butyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylate

HRID 1615472Notes

Reaction equation

HRID 1615472 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.[O:22]=[C:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:24]1.[Cl-].[NH4+]>O1CCCC1>[NH2:11][C:6]1[C:5]2=[CH:4][CH:3]=[C:2]([C:23]3([OH:22])[CH2:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[CH2:24]3)[N:10]2[N:9]=[CH:8][N:7]=1

Participants

7

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 25517Ammonium ChlorideHCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 422813837-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amineHCID 178418918HCID 178418918, compound

Product 1

HCID 58529617Tert-butyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylateYield 42.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (3.0 g, 14 mmol) in tetrahydrofuran (75 mL) was added chlorotrimethylsilane (4.5 mL, 35 mmol) dropwise. The reaction mixture was stirred at room temperature for 3 hours and a 2M solution of 2-propylmagnesium chloride in THF (37 mL, 74 mmol) was added dropwise. After 3 hours, tert-butyl 3-oxopiperidine-1-carboxylate (5.6 g, 28 mmol) was added in one portion. The mixture was stirred at room temperature overnight at which time LC/MS indicated the reaction was complete. The reaction was poured over a mixture of ice and saturated aqueous ammonium chloride (500 mL). The mixture was allowed to warm to room temperature and was extracted with ethyl acetate (250 mL) four times. The combined organic layers were washed with saturated brine, dried over sodium sulfate and concentrated under reduced pressure. The crude solid was triturated with a 2:1 mixture of ethyl acetate:heptane to obtain the title compound (2 g) having the following physical data.

Workup

  1. waitAfter 3 hours
  2. stirringThe mixture was stirred at room temperature overnight at which time LC/MS
  3. temperatureto warm to room temperature
  4. extractionwas extracted with ethyl acetate (250 mL) four times
  5. washThe combined organic layers were washed with saturated brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude solid was triturated with a 2:1 mixture of ethyl acetate

Sources & evidence

ORD record
ord-fe52349cc3a04284bdba9075b71ae893
Source dataset
uspto-grants-2014_07
Patent number
US08765754B2

Reaction notes

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