1,3-Dibromo-5,5-dimethylhydantoin → 4-(4-Amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)butan-1-ol
Reaction equation
[NH2:1][C:2]1[C:7]2=[CH:8][CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][CH2:14][OH:15])[N:6]2[N:5]=[CH:4][N:3]=1.[Br:16]N1C(C)(C)C(=O)N(Br)C1=O>O1CCCC1>[NH2:1][C:2]1[C:7]2=[C:8]([Br:16])[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][CH2:14][OH:15])[N:6]2[N:5]=[CH:4][N:3]=1Participants
Conditions
- Temperature
- -20 °C
Procedure
To a cooled (−20° C.) solution of 4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)butan-1-ol (1.20 g, 5.82 mmol) in tetrahydrofuran (30 mL) was added 1,3-dibromo-5,5-dimethylhydantoin (832 mg, 2.91 mmol) in 4 portions over 10 min. The mixture was allowed to stir (−20° C.) for 3 h. The reaction was quenched with the addition saturated aqueous Na2SO3 (30 mL) and was allowed to warm to rt. The mixture was extracted with ethyl acetate (3×25 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated. The crude material was purified by ISCO® chromatography using a gradient of 75% to 100% ethyl acetate in hexanes to afford 1.2 g (72%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 7.81 (s, 1 H), 6.60 (s, 1 H), 4.37 (t, 1H), 3.39 (q, 2 H), 2.80 (t, 2 H), 1.70-1.60 (m, 2 H), 1.48-1.39 (m, 2 H); ES-MS m/z 285.1 [M+H]+, HPLC RT (min) 1.55.
Workup
- customThe reaction was quenched with the addition saturated aqueous Na2SO3 (30 mL)
- temperatureto warm to rt
- extractionThe mixture was extracted with ethyl acetate (3×25 mL)
- washThe combined organics were washed with brine
- dry with materialdried (Na2SO4)
- concentrationconcentrated
- customThe crude material was purified by ISCO® chromatography
Sources & evidence
- ORD record
- ord-913a1cdbd0c247acaaf6bb864aab17a0
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08431695B2
Reaction notes
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