Dimethylformamide → 6-bromo-N-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine

HRID 404542Notes

Reaction equation

HRID 404542 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[NH2:6].[Br:12][C:13]1[N:14]=[C:15](Br)[C:16]2[N:17]([CH:19]=[CH:20][N:21]=2)[CH:18]=1.C(N(CC)C(C)C)(C)C.CN([CH:35]=[O:36])C>>[Br:12][C:13]1[N:14]=[C:15]([NH:6][C:5]2[CH:7]=[C:8]([O:36][CH3:35])[C:9]([O:10][CH3:11])=[C:3]([O:2][CH3:1])[CH:4]=2)[C:16]2[N:17]([CH:19]=[CH:20][N:21]=2)[CH:18]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 227703,4-DimethoxyanilineHCID 81531DiisopropylethylamineHCID 150258436,8-Dibromoimidazo[1,2-a]pyrazine

Product 1

HCID 866449836-bromo-N-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amineYield 74%

Conditions

Temperature
120 °C

Procedure

A mixture of 3,4-dimethoxyaniline (18.0 g, 118 mmol), 6,8-dibromoimidazo[1,2-a]pyrazine (25.0 g, 90.4 mmol), and N,N-diisopropylethylamine (11.7 g, 90.4 mmol) in DMF (500 mL) was stirred at 120° C. overnight. After this time, the reaction was cooled to room temperature and concentrated to approximately 100 mL under reduced pressure. The dark brown reaction mixture was poured into ice-cold water (300 mL) and stirred for 10 min. The resulting brown precipitate was filtered and the filter cake washed with water (100 mL). The filter cake was dried under vacuum and recrystallization from methanol (˜800 mL) to afford 6-bromo-N-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine (2) (23.3 g, 74%) as a light brown needle-shaped solid: 1H NMR (300 MHz, DMSO-d6) 9.81 (s, 1H), 8.22 (s, 1H), 7.93 (s, 1H), 7.75 (d, J=2.4 Hz, 1H), 7.62 (s, 1H), 7.53 (dd, J=8.7, 2.4, 1H), 6.94 (d, J=8.7 Hz, 1H), 3.77 (s, 3H), 3.75 (s, 3H); ESI MS m/z 349.2 [M+H]+; HPLC, 6.92 min, >99% (AUC).

Workup

  1. temperatureAfter this time, the reaction was cooled to room temperature
  2. concentrationconcentrated to approximately 100 mL under reduced pressure
  3. additionThe dark brown reaction mixture was poured into ice-cold water (300 mL)
  4. stirringstirred for 10 min
  5. filtrationThe resulting brown precipitate was filtered
  6. washthe filter cake washed with water (100 mL)
  7. dry with materialThe filter cake was dried under vacuum and recrystallization from methanol (˜800 mL)

Sources & evidence

ORD record
ord-b0a548d551ce421480d23f6b5c4510a5
Source dataset
uspto-grants-2014_06
Patent number
US08748607B2

Reaction notes

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