1,3-Dibromo-5,5-dimethylhydantoin → Tert-butyl 3-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylate
Reaction equation
[NH2:1][C:2]1[C:7]2=[CH:8][CH:9]=[C:10]([C:11]3([OH:24])[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.[Br:25]N1C(C)(C)C(=O)N(Br)C1=O.[O-]S([O-])=O.[Na+].[Na+]>C1COCC1>[NH2:1][C:2]1[C:7]2=[C:8]([Br:25])[CH:9]=[C:10]([C:11]3([OH:24])[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a cooled (−20° C.) solution tert-butyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylate (1.00 g, 3.00 mmol) in THF (16 mL) was added 1,3-dibromo-5,5-dimethylhydantoin (429 mg, 1.50 mmol) in 3 portions over 10 min. The mixture was allowed warm to 0° C. and stirred for 2 h. The mixture was then stirred at rt for 64 h. Saturated, aqueous Na2SO3 (50 mL) was added and the mixture was warmed to rt. The mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried (Na2SO4) and evaporated. The crude mixture was purified via ISCO® chromatography using a gradient of 50 to 75% ethyl acetate in hexanes to afford 892 mg (72%) of the desired product. ES-MS m/z 412.26 [M+H]+, HPLC RT (min) 2.62.
Workup
- stirringThe mixture was then stirred at rt for 64 h
- temperaturethe mixture was warmed to rt
- extractionThe mixture was extracted with ethyl acetate (3×50 mL)
- washThe combined organic layers were washed with brine
- dry with materialdried (Na2SO4)
- customevaporated
- customThe crude mixture was purified via ISCO® chromatography
Sources & evidence
- ORD record
- ord-957d6071febd4cc0924ff84e43aaa9aa
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08431695B2
Reaction notes
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