Chlorotrimethylsilane → 8-(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-1,4-dioxaspiro[4.5]decan-8-ol

7-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (9.20 g, 35.41 mmol) was dissolved in THF (105 mL) under argon at room temperature. Chlorotrimethylsilane (9.08 mL, 7.77 g, 70.82 mmol, 2 eq.) was added, and the mixture was stirred at room temperature for 3 h. It was then cooled to 0° C., and 2-propyl magnesium chloride (74 mL of a 2.0 M solution in THF, 149 mmol, 4.2 eq.) was added. The mixture was stirred for further 3 h while warming up to room temperature. Then, 1,4-dioxaspiro[4.5]decan-8-one (8.38 g, 53.12 mmol, 1.5 eq.) was added, and stirring was continued for another 16 h. The reaction was quenched with a 1:1 mixture of concentrated aqueous ammonium chloride solution and ice until the pH value 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 title compound was crystallized from diethyl ether. Yield: 6.05 g (58% of th.).

1. temperatureIt was then cooled to 0° C.
2. stirringThe mixture was stirred for further 3 h
3. temperaturewhile warming up to room temperature
4. stirringstirring
5. waitwas continued for another 16 h
6. customThe reaction was quenched with a 1:1 mixture of concentrated aqueous ammonium chloride solution and ice until the pH value
7. extractionThe mixture was extracted with two portions of ethyl acetate
8. dry with materialthe combined organic extracts were dried over anhydrous sodium carbonate
9. concentrationconcentrated to dryness
10. customThe title compound was crystallized from diethyl ether

ORD record

ord-69c7c35bce9e40b487c715e1a02256f4

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040691B2