1,3-Dibromo-5,5-dimethylhydantoin → HCID 59231971, compound

HRID 1091492Notes

Reaction equation

[NH2:1][C:2]1[C:7]2=[CH:8][CH:9]=[C:10]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.[Br:24]N1C(C)(C)C(=O)N(Br)C1=O>O1CCCC1>[NH2:1][C:2]1[C:7]2=[C:8]([Br:24])[CH:9]=[C:10]([CH:11]3[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH2:16]3)[N:6]2[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: -20 °C

Procedure

To a cooled (−20° C.) solution of tert-butyl 4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)piperidine-1-carboxylate (660 mg, 2.08 mmol) in tetrahydrofuran (10 mL) was added 1,3-dibromo-5,5-dimethylhydantoin (297 mg, 1.04 mmol) in 3 portions over 10 min. The mixture was allowed to stir (−20° C.) for 1 h. The reaction was quenched with the addition saturated aqueous Na2SO3 (10 mL) and was allowed to warm to rt. The mixture was extracted with ethyl acetate (3×20 mL). The combined organics were washed with brine (25 mL), dried (Na2SO4) and evaporated. The crude material was purified by ISCO® chromatography using a gradient of 75 to 100% ethyl acetate in hexanes to afford 494 mg (60%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 7.83 (s, 1H), 6.64 (s, 1H), 4.10-3.96 (m, 2H), 3.29-3.19 (m, 1H), 1.90 (d, 2H), 1.55-1.42 (m, 2H), 1.41 (s, 9H); ES-MS m/z 396.1 [M+H]+, HPLC RT (min) 2.79.

Workup

customThe reaction was quenched with the addition saturated aqueous Na2SO3 (10 mL)
temperatureto warm to rt
extractionThe mixture was extracted with ethyl acetate (3×20 mL)
washThe combined organics were washed with brine (25 mL)
dry with materialdried (Na2SO4)
customevaporated
customThe crude material was purified by ISCO® chromatography

Sources & evidence

ORD record: ord-90896cfbcb7548db8019e1d82abbae98
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129379B2

Reaction notes

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