Chlorotrimethylsilane → HCID 58529613, compound

HRID 1972760Notes

Reaction equation

HRID 1972760 reaction equation
Cl[Si](C)(C)C.Br[C:7]1[N:15]2[C:10]([C:11]([NH2:16])=[N:12][CH:13]=[N:14]2)=[CH:9][CH:8]=1.CC([Mg]Cl)C.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].[O:35]1CCCC1>ClCCl>[NH2:16][C:11]1[C:10]2=[CH:9][CH:8]=[C:7]([C:32]3([OH:35])[CH2:33][CH2:34][N:29]([C:27]([O:26][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:28])[CH2:30][CH2:31]3)[N:15]2[N:14]=[CH:13][N:12]=1

Participants

7

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 8028Tetrahydrofuran2×HCID 7010304N-(tert-butoxycarbonyl)piperidineHCID 422813837-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amineHCID 178418918HCID 178418918, compound

Product 1

HCID 58529613HCID 58529613, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Chlorotrimethylsilane (89 mL, 0.70 mol) was added drop wise to a stirred solution of 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine in tetrahydrofuran (1.6 L, anhydrous) and stirring was continued for 3 h. The solution was cooled to 0° C. and 2-propyl magnesium chloride solution (2M in THF, 740 mL, 1.48 mol) was slowly added. The reaction was warmed to 25° C. and stirring continued for 2 h, then cooled back down to −5° C. and a solution of N-tert-butoxycarbonyl piperidine (91.0 g, 0.68 mol) in THF (1 L) was added drop wise. The reaction was continued for 18 h at 25° C., then the mixture was, poured into vigorously-stirred ice water (8 L). The aqueous mixture was extracted with ethyl acetate (3×3 L) and the combined organic portions were dried over magnesium sulfate. Filtration and concentration in vacuo gave a dark-orange oil which was dissolved in a minimal volume of dichloromethane and crystallization induced. After cooling (−10° C.) the mixture for several hours, the crystalline product was collected by suction filtration, washed with diethyl ether and dried to give a colorless solid (61 g, 52%). Purification of the filtrate by silica gel chromatography (5% methanol/dichloromethane) yielded additional product (37 g, 32%). 1H-NMR (DMSO-d6) δ 7.77 (s, 1H), 7.69 (br s, 2H), 6.80 (d, 1H), 6.55 (d, 1H), 5.74 (s, 1H), 3.77 (m, 2H), 3.15 (br m, 2H), 2.48 (m, 2H), 1.70 (d, 2H), 1.40 (s, 9H). ES-MS m/z=334.1 [M+H]+, RT (min) 2.15.

Workup

  1. temperatureThe reaction was warmed to 25° C.
  2. stirringstirring
  3. waitcontinued for 2 h
  4. temperaturecooled back down to −5° C.
  5. waitThe reaction was continued for 18 h at 25° C.
  6. additionpoured
  7. extractionThe aqueous mixture was extracted with ethyl acetate (3×3 L)
  8. dry with materialthe combined organic portions were dried over magnesium sulfate
  9. filtrationFiltration and concentration in vacuo
  10. customgave a dark-orange oil which
  11. temperatureAfter cooling (−10° C.) the mixture for several hours
  12. filtrationthe crystalline product was collected by suction filtration
  13. washwashed with diethyl ether
  14. customdried

Sources & evidence

ORD record
ord-9206c78f09e8430bafa9ca51bb223368
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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